Dibenzocycloheptene compound

ABSTRACT

The present invention discloses a dibenzocycloheptene compound represented by the formula (I):  
                 
 
     wherein R 1 : hydrogen atom, halogen atom, etc., R 2  hydrogen atom, halogen atom, etc., A: 5-membered or 6-membered heteroaromatic ring group containing 1 to 3 hetero atom(s) selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, and the heteroaromatic ring group, etc. may have halogen atom, nitrogen atom, etc. as substituent(s),.B: formula; —CH═CH—, formula; —CH 2 O—, etc., Y: C 1 -C 10  alkylene group which may have halogen atom, etc. as substituent(s), etc., Z: carboxyl group which may be protected, etc., m: an integer of 1 to 4, n: an integer of 1 to 3,  
        represents a single bond or a double bond, or a pharmaceutically acceptable salt thereof and a medical composition containing the same as an effective ingredient which has leukotriene C 4  antagonistic action and leukotriene E 4  antagonistic action in addition to potent leukotriene D 4  antagonistic action, and useful as antiasthmatic agent, antiallergic agent and anti-inflammatory agent.

TECHNICAL FIELD

[0001] The present invention relates to a dibenzocycloheptene compound which has, in addition to potent leukotriene D₄ antagonistic action, leukotriene C₄ antagonistic action and leukotriene E₄ antagonistic action, and useful as an antiazma agent, an antiallergic agent and anti-inflammatory agent, or a pharmaceutically acceptable salt thereof.

BACKGROUND ART

[0002] As a compound having leukotriene D₄ antagonistic action similarly in the present invention and having a structure similar to the compound of the present invention, there has been known, for example, a compound disclosed in WO94/19345, and as a compound having a structure partially similar to the same, there have been known 5-[3-[3-(2quinolinylmethoxy)phenoxy]propyl]-1H-tetrazole (RG7152; J. Med. Chem., 33, 1186 (1990)), 5-[[2-[[4-(2-quinolinylmethoxy)phenoxy]methyl]phenyl]methyl]-1H-tetrazole (RG12525; J. Med. Chem., 33, 1194 (1990)), and a compound disclosed in WO95/18107.

[0003] In the present invention, as a result of research for long years about syntheses of compounds having potent leukotriene D₄ antagonistic action, as well as having antagonistic actions to leukotriene C₄ and leukotriene E₄ and their pharmaceutical effects, the inventors have found that novel dibenzocycloheptene compounds have excellent leukotriene D₄ antagonistic action, as well as having leukotriene C₄ and leukotriene E₄ antagonistic action with good balance, and have high safety, excellent oral absorbability and durability of the action to accomplish the present invention.

SUMMARY OF THE INVENTION

[0004] The present invention relates to a dibenzocycloheptene compound represented by the formula (I):

[0005] wherein R¹ represents a hydrogen atom, a halogen atom, a hydroxy group, a nitro group, a cyano group, a carbamoyl group, a formyl group, a carboxyl group, a 1H-tetrazol-5-yl group, a C₁-C₄ alkyl group, a fluoro C₁-C₄ alkyl group, a hydroxy C₁-C₄ alkyl group, a C₂-C₄ alkenyl group, a C₂-C₄ alkynyl group, a C₁-C₄ alkoxy group, a fluoro C₁-C₄ alkoxy group, a C₁-C₄ alkylthio group, a C₁-C₄ alkylsulfinyl group or a C₁-C₄ alkylsulfonyl group, R² represents a hydrogen atom, a halogen atom, a nitro group, a cyano group, a C₁-C₄ alkyl group or a C₁-C₄ alkoxy group, A represents a 5-membered or 6-membered heteroaromatic ring group containing 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom or a fused heteroaromatic ring group in which the heteroaromatic ring group and a benzene ring are fused, the heteroaromatic ring group or fused heteroaromatic ring group may have a substituent(s) selected from a halogen atom, a nitro group, a cyano group, a C₁-C₄ alkyl group, a fluoro C₁-C₄ alkyl group, a C₁-C₄ alkoxy group, a fluoro C₁-C₄ alkoxy group, a C₁-C₄ alkylthio group or a C₃-C₄ alkylene group, B represents a formula: —CH═CH—, —CH₂O—, —CH₂CH₂—, —CH₂S—, —OCH₂— or —SCH₂—, X represents an oxygen atom, a sulfur atom, methylene group or a formula: ═CH—, Y represents a C₁-C₁₀ alkylene group which may have a substituent(s) selected from a halogen atom, C₁-C₄ alkyl group and C₁-C₄ alkoxy group, or a group represented by the formula (a):

[0006] wherein o and p each represent an integer of 0 to 2, and q represents an integer of 1 to 4,

[0007] Z represents a carboxyl group which may be protected; 1H-tetrazol-5-yl group; the formula —NH—SO₂—R³; or the formula —CO—NH—SO₂—R³

[0008] wherein R³ represents a C₁-C₄ alkyl group, a fluoro C₁-C₄ alkyl group or a phenyl group which may have a halogen atom, a C₁-C₄ alkyl group, a fluoro C₁-C₄ alkyl group, a C₁-C₄ alkoxy group, a fluoro C₁-C₄ alkoxy group, a nitro group or a cyano group as a substituent(s),

[0009] m is an integer of 1 to 4, when m is 2 or more, a plural number of R¹ may be different from each other, n is an integer of 1 to 3, and when n is 2 or more, a plural number of R² may be different from each other,

[0010]

represents a single bond or a double bond, or a pharmaceutically acceptable salt thereof.

BEST MODE FOR CARRYING OUT THE INVENTION

[0011] In the compound represented by the above-mentioned formula (I), as the halogen atom of R¹, there may be mentioned, for example, a fluorine atom, a chlorine atom, bromine atom or iodine atom, preferably a fluorine atom, a chlorine atom or bromine atom, more preferably a fluorine atom or a chlorine atom.

[0012] As the C₁-C₄ alkyl group of R¹, there may be mentioned, for example, a straight or branched C₁-C₄ alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or t-butyl group, preferably methyl, ethyl, propyl or isopropyl group, more preferably methyl or ethyl group, particularly preferably methyl group.

[0013] As the fluoro C₁-C₄ alkyl group of R¹, there may be mentioned, for example, a straight or branched C₁-C₄ alkyl group substituted by 1 to 3 fluorine atoms such as fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2-fluoropropyl, 3-fluoropropyl or 4-fluorobutyl group, preferably fluoromethyl, difluoromethyl, trifluoromethyl or 2-fluoroethyl group, more preferably fluoromethyl, difluoromethyl or trifluoromethyl group, particularly preferably difluoromethyl or trifluoromethyl group.

[0014] As the hydroxy C₁-C₄ alkyl group of R¹, there may be mentioned, for example, a straight or branched C₁-C₄ alkyl group substituted by hydroxy group such as a hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxy-1-methylethyl, 1-hydroxypropyl, 2-hydroxypropyl, 3-hydroxypropyl, 1-hydroxybutyl or 4-hydroxybutyl group, preferably hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxy-1-methylethyl, 1-hydroxypropyl or 2-hydroxypropyl group, more preferably hydroxymethyl, 1-hydroxyethyl, 1-hydroxy-1-methylethyl or 1-hydroxypropyl group, particularly preferably hydroxymethyl or 1-hydroxy-1-methylethyl group.

[0015] As the C₂-C₄ alkenyl group of R¹, there may be mentioned, for example, a straight or branched C₂-C₄ alkenyl group such as vinyl, 1-propenyl, allyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl or 2-methyl-2-propenyl group, preferably vinyl, 1-propenyl, allyl, 1-butenyl, 2-butenyl or 2methyl-1-propenyl group, more preferably vinyl, 1-propenyl or allyl group, particularly preferably vinyl group.

[0016] As the C₂-C₄ alkynyl group of R¹, there may be mentioned, for example, a straight C₂-C₄ alkynyl group such as ethynyl, 1-propynyl, propargyl, 1-butynyl, 2-butynyl or 3-butynyl group, preferably ethynyl, 1-propynyl or 1-butynyl group, more preferably ethynyl or 1-propynyl group, particularly preferably ethynyl group.

[0017] As the C₁-C₄ alkoxy group of R¹, there may be mentioned, for example, a straight or branched C₁-C₄ alkoxy group such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy or t-butoxy group, preferably methoxy, ethoxy, propoxy or isopropoxy group, more preferably methoxy or ethoxy group, particularly preferably methoxy group.

[0018] As the fluoro C₁-C₄ alkoxy group of R¹, there may be mentioned, for example, a straight or branched C₁-C₄ alkoxy group substituted by 1 to 3 fluorine atoms such as fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethoxy, 2, 2, 2-trifluoroethoxy, 2-fluoropropoxy, 3-fluoropropoxy or 4-fluorobutoxy group, preferably fluoromethoxy, difluoromethoxy, trifluoromethoxy or 2-fluoroethoxy group, more preferably fluoromethoxy, difluoromethoxy or trifluoromethoxy group, particularly preferably difluoromethoxy or trifluoromethoxy group.

[0019] As the C₁-C₄ alkylthio group of R¹, there may be mentioned, for example, a straight or branched C₁-C₄ alkylthio group such as methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, sec-butylthio or t-butylthio group, preferably methylthio, ethylthio, propylthio or isopropylthio group, more preferably methylthio or ethylthio group, particularly preferably methylthio group.

[0020] As the C₁-C₄ alkylsulfinyl group of R¹, there may be mentioned, for example, a straight or branched C₁-C₄ alkylsulfinyl group such as methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or t-butylsulfinyl group, preferably methylsulfinyl, ethylsulfinyl, propylsulfinyl or isopropylsulfinyl group, more preferably methylsulfinyl or ethylsulfinyl group, particularly preferably methylsulfinyl group.

[0021] As the C₁-C₄ alkylsulfonyl group of R¹, there may be mentioned, for example, a straight or branched C₁-C₄ alkylsulfonyl group such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or t-butylsulfonyl group, preferably methylsulfonyl, ethylsulfonyl, propylsulfonyl or isopropylsulfonyl group, more preferably methylsulfonyl or ethylsulfonyl group, particularly preferably methylsulfonyl group.

[0022] In particular, as R¹ in the formula (I), there may be preferably mentioned a hydrogen atom, a fluorine atom, a chlorine atom, bromine atom, a hydroxy group, a nitro group, a cyano group, a carbamoyl group, a formyl group, a carboxyl group, 1H-tetrazol-5-yl group, methyl group, ethyl group, propyl group, isopropyl group, fluoromethyl group, difluoromethyl group, trifluoromethyl group, 2-fluoroethyl group, hydroxymethyl group, 1-hydroxyethyl group, 2-hydroxyethyl group, 1-hydroxy-1-methylethyl group, 1-hydroxypropyl group, 2-hydroxypropyl group, vinyl group, 1-propenyl group, allyl group, 1-butenyl group, 2-butenyl group, 2-methyl-1-propenyl group, ethynyl group, 1-propynyl group, 1-butynyl group, methoxy group, ethoxy group, propoxy group, isopropoxy group, fluoromethoxy group, difluoromethoxy group, trifluoromethoxy group, 2-fluoroethoxy group, methylthio group, ethylthio group, propylthio group, isopropylthio group, methylsulfinyl group, ethylsulfinyl group, propylsulfinyl group, isopropylsulfinyl group, methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group or isopropylsulfonyl group, more preferably a hydrogen atom, a fluorine atom, a chlorine atom, a hydroxy group, a nitro group, a cyano group, a carbamoyl group, a formyl group, 1H-tetrazol-5-yl group, methyl group, ethyl group, fluoromethyl group, difluoromethyl group, trifluoromethyl group, hydroxymethyl group, 1-hydroxyethyl group, 1-hydroxy-1-methylethyl group, 1-hydroxypropyl group, vinyl group, 1-propenyl group, allyl group, ethynyl group, 1-propynyl group, 1-butynyl group, methoxy group, ethoxy group, fluoromethoxy group, difluoromethoxy group, trifluoromethoxy group, methylthio group, ethylthio group, methylsulfinyl group, ethylsulfinyl group, methylsulfonyl group or ethylsulfonyl group, further more preferably hydrogen atom, fluorine atom, chlorine atom, nitro group, cyano group, formyl group, 1H-tetrazol-5-yl group, methyl group, difluoromethyl group, trifluoromethyl group, hydroxymethyl group, 1-hydroxy-1-methylethyl group, vinyl group, ethynyl group, methoxy group, difluoromethoxy group, trifluoromethoxy group, methylthio group, methylsulfinyl group or methylsulfonyl group, particularly preferably hydrogen atom, fluorine atom, chlorine atom, cyano group, trifluoromethyl group, hydroxymethyl group, 1hydroxy-1-methylethyl group, ethynyl group, methoxy group, difluoromethoxy group, trifluoromethoxy group, methylsulfinyl group or methylsulfonyl group.

[0023] In the formula (I), a halogen atom, C₁-C₄ alkyl group and C₁-C₄ alkoxy group of R² have the same meanings as those of the above-mentioned R¹, and as R², there may be preferably mentioned hydrogen atom, fluorine atom, chlorine atom, bromine atom, nitro group, cyano group, methyl group, ethyl group, propyl group, isopropyl group, methoxy group, ethoxy group, propoxy group or isopropoxy group, more preferably hydrogen atom, fluorine atom, chlorine atom, nitro group, cyano group, methyl group, ethyl group, methoxy group or ethoxy group, further more preferably hydrogen atom, fluorine atom, chlorine atom, methyl group or methoxy group, particularly preferably hydrogen atom.

[0024] In the formula (I), “a 5-membered or 6-membered heteroaromatic ring group containing 1 to 3 hetero atom(s) selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom or a fused heteroaromatic ring group in which the heteroaromatic ring group and a benzene are fused” of A, there may be mentioned, for example, a 5-membered heteroaromatic ring group such as furan, thiophen, oxazol, thiazol, imidazol, pyrazol or thiadiazol group; a 6-membered heteroaromatic ring group such as pyridin, pyrimidin, pyridazin or pyrazin group; or a fused heteroaromatic ring group such as benzofuran, benzothiophen, benzoxazol, benzothiazol, benzimidazol, quinolin, quinazolin or quinoxalin group, preferably oxazol, thiazol, imidazol, pyrazol, thiadiazol, pyridine, pyrimidin, pyridazin, pyrazin, benzoxazol, benzothiazol, benzimidazol, quinolin, quinazolin or quinoxalin group, more preferably thiazol, thiadiazol, pyridine, pyrimidin, benzoxazol, benzothiazol, quinolin or quinazolin group, particularly preferably pyridine, benzothiazol or quinolin group.

[0025] The above-mentioned heteroaromatic ring group or fused heteroaromatic ring group may have a substituent(s), and as the substituent(s), there may be mentioned, for example, a halogen atom with the same meaning as R¹; a C₁-C₄ alkyl group with the same meaning as R¹; a fluoro C₁-C₄ alkyl group with the same meaning as R¹; a C₁-C₄ alkoxy group with the same meaning as R¹; a fluoro C₁-C₄ alkoxy group with the same meaning as R¹; a C₁-C₄ alkylthio group with the same meaning as R¹; nitro group; cyano group; or a C₃-C₄ alkylene group such as trimethylene, tetramethylene group (said alkylene group bonds to an adjacent carbon atom on the heteroaromatic ring to form a 5-membered ring or 6-membered ring), preferably fluorine atom, chlorine atom, bromine atom, nitro, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, methoxy, ethoxy, propoxy, isopropoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethoxy, methylthio, ethylthio, propylthio, isopropylthio, trimethylene or tetramethylene group, more preferably a fluorine atom, a chlorine atom, nitro, cyano, methyl, ethyl, isopropyl, t-butyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, methylthio, ethylthio, trimethylene or tetramethylene group, further more preferably fluorine atom, chlorine atom, nitro, cyano, methyl, isopropyl, t-butyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, methylthio or tetramethylene group, particularly preferably fluorine atom, chlorine atom, trifluoromethyl or tetramethylene group.

[0026] A number of the substituent(s) on the heteroaromatic ring group or fused heteroaromatic ring group is 1 to 4, preferably 1 to 2.

[0027] As A in the formula (I), it is specifically mentioned, preferably 2-oxazolyl, 2-thiazolyl, 2- or 4-imidazolyl, 3-pyrazolyl, 1,3,4-thiadiazol-2-yl, 2-pyridyl, 2- or 4-pyrimidinyl, 3-pyridazinyl, 2-pyrazinyl, 2-benzoxazolyl, 2-benzothiazolyl, 2-benzoimidazolyl, quinolin-2-yl, quinazolin-2-yl, quinoxalin-2-yl, 4-methyl-2-thiazolyl, 4-ethyl-2-thiazolyl, 4-isopropyl-2-thiazolyl, 4-t-butyl-2-thiazolyl, 4-trifluoromethyl-2-thiazolyl, 5-methyl-1,3,4-thiadiazol-2-yl, 5-ethyl-1,3,4-thiadiazol-2-yl, 5-isopropyl-1,3,4-thiadiazol-2-yl, 5-t-butyl-1,3,4-thiadiazol-2-yl, 5-trifluoromethyl-1,3,4-thiadiazol-2-yl, 5,6-difluoro-2-pyridyl, 5,6-dichloro-2-pyridyl, 5,6-dimethyl-2-pyridyl, 5,6-diethyl-2-pyridyl, 6-trifluoromethyl-2-pyridyl, 6-methylthio-2-pyridyl, 5H-6,7-dihydrocyclopenta[b]pyridin-2-yl, 5,6,7,8-tetrahydroquinolin-2-yl, 5,6-difluoro-2-pyrimidinyl, 5,6-dichloro-2-pyrimidinyl, 5,6-dimethyl-2-pyrimidinyl, 6-trifluoromethyl-2-pyrimidinyl, 5H-6,7-dihydrocyclopenta[d]pyrimidin-2-yl, 5,6,7,8-tetrahydroquinazolin-2-yl, 6-fluoro-2-benzoxazolyl, 5-fluoro-2-benzoxazolyl, 5,6-difluoro-2-benzoxazolyl, 6-chloro-2-benzoxazolyl, 5-chloro-2-benzoxazolyl, 5,6-dichloro-2-benzoxazolyl, 5-chloro-6-fluoro-2-benzoxazolyl, 5-methyl-2-benzoxazolyl, 5-cyano-2-benzoxazolyl, 5-trifluoromethyl-2-benzoxazolyl, 5-methylthio-2-benzoxazolyl, 6-fluoro-2-benzothiazolyl, 5-fluoro-2-benzothiazolyl, 5,6-difluoro-2-benzothiazolyl, 6-chloro-2-benzothiazolyl, 5-chloro-2-benzothiazolyl, 5,6-dichloro-2-benzothiazolyl, 5-chloro-6-fluoro-2-benzothiazolyl, 5-methyl-2-benzothiazolyl, 5-cyano-2-benzothiazolyl, 5-trifluoromethyl-2-benzothiazolyl, 5-methylthio-2-benzothiazolyl, 5-fluoroquinolin-2-yl, 6-fluoroquinolin-2-yl, 7-fluoroquinolin-2-yl, 5-chloroquinolin-2-yl, 6-chloroquinolin-2-yl, 7-chloroquinolin-2-yl, 7-methylquinolin-2-yl, 7-trifluoromethylquinolin-2-yl, 7-methoxyquinolin-2-yl, 7-difluoromethoxyquinolin-2-yl, 7-trifluoromethoxyquinolin-2-yl, 5,7-difluoroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 5,7-dichloroquinolin-2-yl, 6,7-dichloroquinolin-2-yl, 5-chloro-7-fluoroquinolin-2-yl, 6-chloro-7-fluoroquinolin-2-yl, 7-chloro-5-fluoroquinolin-2-yl, 7-chloro-6-fluoroquinolin-2-yl, 7-chloro-6-cyanoquinolin-2-yl, 7-cyano-6-fluoroquinolin-2-yl, 6-fluoro-7-trifluoromethylquinolin-2-yl, 5,6,7-trifluoroquinolin-2-yl, 5-fluoroquinazolin-2-yl, 6-fluoroquinazolin-2-yl, 7-fluoroquinazolin-2-yl, 5-chloroquinazolin-2-yl, 6-chloroquinazolin-2-yl, 7-chloroquinazolin-2-yl, 7-methylquinazolin-2-yl, 7-trifluoromethylquinazolin-2-yl, 7-methoxyquinazolin-2-yl, 7-difluoromethoxyquinazolin-2-yl, 7-trifluoromethoxyquinazolin-2-yl, 5,7-difluoroquinazolin-2-yl, 6,7-difluoroquinazolin-2-yl, 5,7-dichloroquinazolin-2-yl, 6,7-dichloroquinazolin-2-yl, 5-chloro-7-fluoroquinazolin-2-yl, 6-chloro-7-fluoroquinazolin-2-yl, 7-chloro-5-fluoroquinazolin-2-yl, 7-chloro-6-fluoroquinazolin-2-yl, 7-chloro-6-cyanoquinazolin-2-yl, 7-cyano-6-fluoroquinazolin-2-yl, 6-fluoro-7-trifluoromethylquinazolin-2-yl or 5,6,7-trifluoroquinazolin-2-yl group, more preferably 2-thiazolyl, 1,3,4-thiadiazol-2-yl, 2-pyridyl, 2-pyrimidinyl, 2-benzoxazolyl, 2-benzothiazolyl, quinolin-2-yl, quinazolin-2-yl, 4-methyl-2-thiazolyl, 4-isopropyl-2-thiazolyl, 4-t-butyl-2-thiazolyl, 4-trifluoromethyl-2-thiazolyl, 5-methyl-1,3,4-thiadiazol-2-yl, 5-isopropyl-1,3,4-thiadiazol-2-yl, 5-t-butyl-1,3,4-thiadiazol-2-yl, 5-trifluoromethyl-1,3,4-thiadiazol-2-yl, 5,6-difluoro-2-pyridyl, 5,6-dichloro-2-pyridyl, 5,6-dimethyl-2-pyridyl, 5H-6,7-dihydrocyclopenta[b]pyridin-2-yl, 5,6,7,8-tetrahydroquinolin-2-yl, 5,6-difluoro-2-pyrimidinyl, 5,6-dichloro-2-pyrimidinyl, 5,6-dimethyl-2-pyrimidinyl, 6-trifluoromethyl-2-pyrimidinyl, 5H-6,7-dihydrocyclopenta[d]pyrimidin-2-yl, 5,6,7,8-tetrahydroquinazolin-2-yl, 6-fluoro-2-benzoxazolyl, 5-fluoro-2-benzoxazolyl, 5,6-difluoro-2-benzoxazolyl, 6-chloro-2-benzoxazolyl, 5-chloro-2-benzoxazolyl, 5,6-dichloro-2-benzoxazolyl, 5-chloro-6-fluoro-2-benzoxazolyl, 5-methyl-2-benzoxazolyl, 5-cyano-2-benzoxazolyl, 5-trifluoromethyl-2-benzoxazolyl, 5-methylthio-2-benzoxazolyl, 6-fluoro-2-benzothiazolyl, 5-fluoro-2-benzothiazolyl, 5,6-difluoro-2-benzothiazolyl, 6-chloro-2-benzothiazolyl, 5-chloro-2-benzothiazolyl, 5,6-dichloro-2-benzothiazolyl, 5-chloro-6-fluoro-2-benzothiazolyl, 5-methyl-2-benzothiazolyl, 5-cyano-2-benzothiazolyl, 5-trifluoromethyl-2-benzothiazolyl, 5-methylthio-2-benzothiazolyl, 5-fluoroquinolin-2-yl, 6-fluoroquinolin-2-yl, 7-fluoroquinolin-2-yl, 5-chloroquinolin-2-yl, 6-chloroquinolin-2-yl, 7-chloroquinolin-2-yl, 7-methylquinolin-2-yl, 7-trifluoromethylquinolin-2-yl, 7-methoxyquinolin-2-yl, 7-difluoromethoxyquinolin-2-yl, 7-trifluoromethoxyquinolin-2-yl, 5,7-difluoroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 5,7-dichloroquinolin-2-yl, 6,7-dichloroquinolin-2-yl, 5-chloro-7-fluoroquinolin-2-yl, 6-chloro-7-fluoroquinolin-2-yl, 7-chloro-5-fluoroquinolin-2-yl, 7-chloro-6-fluoroquinolin-2-yl, 7-chloro-6-cyanoquinolin-2-yl, 7-cyano-6-fluoroquinolin-2-yl, 6-fluoro-7-trifluoromethylquinolin-2-yl, 5,6,7-trifluoroquinolin-2-yl, 5-fluoroquinazolin-2-yl, 6-fluoroquinazolin-2-yl, 7-fluoroquinazolin-2-yl, 5-chloroquinazolin-2-yl, 6-chloroquinazolin-2-yl, 7-chloroquinazolin-2-yl, 7-methylquinazolin-2-yl, 7-trifluoromethylquinazolin-2-yl, 7-methoxyquinazolin-2-yl, 7-difluoromethoxyquinazolin-2-yl, 7-trifluoromethoxyquinazolin-2-yl, 5,7-difluoroquinazolin-2-yl, 6,7-difluoroquinazolin-2-yl, 5,7-dichloroquinazolin-2-yl, 6,7-dichloroquinazolin-2-yl, 5-chloro-7-fluoroquinazolin-2-yl, 6-chloro-7-fluoroquinazolin-2-yl, 7-chloro-5-fluoroquinazolin-2-yl, 7-chloro-6-fluoroquinazolin-2-yl, 7-chloro-6-cyanoquinazolin-2-yl, 7-cyano-6-fluoroquinazolin-2-yl, 6-fluoro-7-trifluoromethylquinazolin-2-yl or 5,6,7-trifluoroquinazolin-2-yl group, further more preferably 2-pyridyl, 2-benzothiazolyl, quinolin-2-yl, 5,6-difluoro-2-pyridyl, 5,6-dichloro-2-pyridyl, 5,6-dimethyl-2-pyridyl, 5,6,7,8-tetrahydroquinolin-2-yl, 6-fluoro-2-benzothiazolyl, 5-fluoro-2-benzothiazolyl, 5,6-difluoro-2-benzothiazolyl, 6-chloro-2-benzothiazolyl, 5-chloro-2-benzothiazolyl, 5,6-dichloro-2-benzothiazolyl, 5-chloro-6-fluoro-2-benzothiazolyl, 5-methyl-2-benzothiazolyl, 5-cyano-2-benzothiazolyl, 5-trifluoromethyl-2-benzothiazolyl, 5-methylthio-2-benzothiazolyl, 5-fluoroquinolin-2-yl, 6-fluoroquinolin-2-yl, 7-fluoroquinolin-2-yl, 5-chloroquinolin-2-yl, 6-chloroquinolin-2-yl, 7-chloroquinolin-2-yl, 7-methylquinolin-2-yl, 7-trifluoromethylquinolin-2-yl, 7-methoxyquinolin-2-yl, 7-difluoromethoxyquinolin-2-yl, 7-trifluoromethoxyquinolin-2-yl, 5,7-difluoroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 5,7-dichloroquinolin-2-yl, 6,7-dichloroquinolin-2-yl, 5-chloro-7-fluoroquinolin-2-yl, 6-chloro-7-fluoroquinolin-2-yl, 7-chloro-5-fluoroquinolin-2-yl, 7-chloro-6-fluoroquinolin-2-yl, 7-chloro-6-cyanoquinolin-2-yl, 7-cyano-6-fluoroquinolin-2-yl, 6-fluoro-7-trifluoromethylquinolin-2-yl or 5,6,7-trifluoroquinolin-2-yl group, particularly preferably 5,6,7,8-tetrahydroquinolin-2-yl, 7-fluoroquinolin-2-yl, 7-chloroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 6,7-dichloroquinolin-2-yl or 7-chloro-6-fluoroquinolin-2-yl.

[0028] In the above-mentioned formula (I), B is, for example, a formula: —CH═CH—, a formula: —CH₂O—, a formula: —CH₂CH₂—, a formula: —CH₂S—, a formula: —OCH₂— or a formula: —SCH₂—, preferably a formula: —CH=CH—, a formula: —OCH₂— or a formula: —CH₂O—.

[0029] In the above-mentioned formula (I), X is an oxygen atom, a sulfur atom, a methylene group or a formula: ═CH—, preferably an oxygen atom or a sulfur atom.

[0030] As the C₁-C₁₀ alkylene group of Y in the above-mentioned formula (I), there may be mentioned, for example, a straight C₁-C₁₀ alkylene group such as methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene, octamethylene, nonamethylene or decamethylene group, preferably a C₁-C₆ alkylene group, more preferably a C₁-C₄ alkylene group,

[0031] particularly preferably methylene, ethylene or trimethylene group.

[0032] Said alkylene group may have a substituent(s), and a halogen atom, a C₁-C₄ alkyl group and a C₁-C₄ alkoxy group as said substituent(s) thereof have the same meanings as those mentioned in the above-mentioned R¹, respectively.

[0033] As the substituent(s) for the alkylene group of Y, there may be preferably mentioned fluorine atom, chlorine atom, methyl, ethyl, propyl, methoxy, ethoxy or propoxy group, more preferably fluorine atom, methyl, ethyl or methoxy group, particularly preferably fluorine atom or methyl group.

[0034] As the group represented by the formula (a) of Y, there may be preferably mentioned a group wherein o=0, p=0 and q=1 (hereinafter referred to as (a-1) group), a group wherein o=0, p=1 and q=1 (hereinafter referred to as (a-2) group), a group wherein o=0, p=1 and q=2 (hereinafter referred to as (a-3) group), a group wherein o=1, p=0 and q=1 (hereinafter referred to as (a-4) group), a group wherein o=1, p=1 and q=1 (hereinafter referred to as (a-5) group), a group wherein o=1, p=1 and q=2 (hereinafter referred to as (a-6) group) or a group wherein o=1, p=1 and q=3 (hereinafter referred to as (a-7) group), more preferably a (a-4) group, a (a-5) group or a (a-6) group, particularly more preferably (a-5) group.

[0035] As the preferred group of Y in the formula (I), there may be specifically mentioned methylene, ethylene, trimethylene, tetramethylene, pentamethylene, fluoromethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, ethylidene, 1-methylethylene, 2-methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethylene, 1-methoxyethylene, 2-methoxyethylene, 1-fluorotrimethylene, 2-fluorotrimethylene, 3-fluorotrimethylene, 1,1-difluorotrimethylene, 2,2-difluorotrimethylene, 3,3-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, 2,2-diethyltrimethylene, 2-methoxytrimethylene, 3-methoxytrimethylene, 2,2-dimethoxytrimethylene, 3,3-dimethoxytrimethylene, (a-1) group, (a-2) group, (a-3) group, (a-4) group, (a-5) group or (a-6) group, more preferably methylene, ethylene, trimethylene, fluoromethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, ethylidene, 1-methylethylene, 2-methylethylene, 1-fluorotrimethylene, 2-fluorotrimethylene, 3-fluorotrimethylene, 1,1-difluorotrimethylene, 2,2-difluorotrimethylene, 3,3-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, (a-4) group, (a-5) group or (a-6) group, further more preferably methylene, ethylene, trimethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, ethylidene, 1-methylethylene, 2-methylethylene, 2,2-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene or (a-5) group, particularly preferably methylene, ethylene, trimethylene, ethylidene, 1-methylethylene, 2-methylethylene or (a-5) group.

[0036] In a group of the formula: —NH—SO₂—R³ or the formula: —CO—NH—SO₂—R³ group shown by Z, C₁-C₄ alkyl group of R³; a fluoro C₁-C₄ alkyl group of R³; or a halogen atom, C₁-C₄ alkyl group, fluoro C₁-C₄ alkyl group, C₁-C₄ alkoxy group or fluoro C₁-C₄ alkoxy group which is a substituent(s) on a phenyl group of R³ have the same meanings as those mentioned in the above-mentioned R¹, respectively.

[0037] As R³, there may be preferably mentioned methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2, 2, 2-trifluoroethyl, phenyl, (o-, m- or p-)fluorophenyl, (o-, m- or p-)chlorophenyl, (o-, m- or p-)methylphenyl, (o-, m- or p-)ethylphenyl, (o-, m- or p-)(trifluoromethyl)phenyl, (o-, m- or p-)methoxyphenyl, (o-, m- or p-)ethoxyphenyl, (o-, m- or p-)(difluoromethoxy)phenyl, (o-, m- or p-)(trifluoromethoxy)phenyl, (o-, m- or p-)nitrophenyl or (o-, m- or p-)cyanophenyl group, more preferably methyl, ethyl, trifluoromethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, phenyl, (o- or p-)fluorophenyl, (o- or p-)chlorophenyl, (o- or p-)methylphenyl, (o- or p-)(trifluoromethyl)phenyl, (o- or p-)methoxyphenyl, (o- or p-)(difluoromethoxy)phenyl, (o- or p-)(trifluoromethoxy)phenyl, (o- or p-)nitrophenyl or (o- or p-)cyanophenyl group, further more preferably methyl, ethyl, trifluoromethyl, phenyl, p-fluorophenyl, p-chlorophenyl, (o- or p-)methylphenyl, p-(trifluoromethyl)phenyl, (o- or p-)methoxyphenyl, p-(difluoromethoxy)phenyl, p-(trifluoromethoxy)phenyl, p-nitrophenyl or p-cyanophenyl group, particularly preferably methyl, trifluoromethyl, phenyl, o-methylphenyl or p-methylphenyl group.

[0038] As a preferred group of Z in the formula (I), there may be specifically mentioned carboxy, 1H-tetrazol-5-yl, methanesulfonylamino, ethanesulfonylamino, trifluoromethanesulfonylamino, phenylsulfonylamino, p-fluorophenylsulfonylamino, p-chlorophenylsulfonylamino, o-methylphenylsulfonylamino, p-methylphenylsulfonylamino, p-trifluoromethylphenylsulfonylamino, o-methoxyphenylsulfonylamino, p-methoxyphenylsulfonylamino, p-difluoromethoxyphenylsulfonylamino, p-trifluoromethoxyphenylsulfonylamino, p-nitrophenylsulfonylamino, p-cyanophenylsulfonylamino, methanesulfonylaminocarbonyl, ethanesulfonylaminocarbonyl, trifluoromethanesulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, p-fluorophenylsulfonylaminocarbonyl, p-chlorophenylsulfonylaminocarbonyl, o-methylphenylsulfonylaminocarbonyl, p-methylphenylsulfonylaminocarbonyl, p-trifluoromethylphenylsulfonylaminocarbonyl, o-methoxyphenylsulfonylaminocarbonyl, p-methoxyphenylsulfonylaminocarbonyl, p-difluoromethoxyphenylsulfonylaminocarbonyl, p-trifluoromethoxyphenylsulfonylaminocarbonyl, p-nitrophenylsulfonylaminocarbonyl or p-cyanophenylsulfonylaminocarbonyl group, more preferably carboxy, 1H-tetrazol-5-yl, methanesulfonylamino, trifluoromethanesulfonylamino, phenylsulfonylamino, o-methylphenylsulfonylamino, p-methylphenylsulfonylamino, methanesulfonylaminocarbonyl, trifluoromethanesulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, o-methylphenylsulfonylaminocarbonyl or p-methylphenylsulfonylaminocarbonyl group, further more preferably carboxy, methanesulfonylamino, trifluoromethanesulfonylamino, methanesulfonylaminocarbonyl or trifluoromethanesulfonylaminocarbonyl group, particularly preferably carboxyl group.

[0039] Incidentally, when Z is a carboxyl group, the carboxyl group may be protected by a protective group. As the protective group, it is not specifically limited so long as it can be easily deprotected in a living body to be changed to a carboxyl group, and there may be mentioned, for example, a C₁-C₄ alkyl group having the same meanings as those defined in R¹; a C₇-C₁₀ aralkyl group such as benzyl, phenylethyl or phenylpropyl group; a C₁-C₄ alkyl group substituted by a C₂-C₅ alkanoyloxy group, such as acetoxymethyl, 1-acetoxyethyl, 1-acetoxypropyl, 1-acetoxybutyl, propanoyloxymethyl, 1-propanoyloxyethyl, butanoyloxymethyl, 1-butanoyloxymethyl, pivaloyloxymethyl, 1-pivaloyloxyethyl, 1-pivaloyloxypropyl or 1-pivaloyloxybutyl group; a C₁-C₄ alkyl group substituted by a (C₁-C₄ alkoxy)carbonyloxy group, such as methoxycarbonyloxymethyl, 1-(methoxycarbonyloxy)ethyl, ethoxycarbonyloxymethyl, 1-(ethoxycarbonyloxy)ethyl, propoxycarbonyloxymethyl, oxymethylcarbonyloxymethyl, 1-(isopropoxycarbonyloxy)ethyl, butoxycarbonyloxymethyl, 1-(butoxycarbonyloxy)ethyl, t-butoxycarbonyloxymethyl or 1-(t-butoxycarbonyloxy)ethyl group; a C₁-C₄ alkyl group substituted by a N,N-di(C₁-C₄ alkyl)aminocarbonyl group such as N,N-dimethylaminocarbonylmethyl, 2-(N,N-dimethylaminocarbonyl)ethyl or N,N-diethylaminocarbonylmethyl group; a C₁-C₄ alkyl group substituted by a N,N-di(C₁-C₄ alkyl)amino group or a 5- to 6-membered cyclic amino group which may contain an oxygen atom such as 2-(N,N-dimethylamino)ethyl, 2-(N,N-diethylamino)ethyl, 3-(N,N-dimethylamino)propyl, 2-piperidinoethyl, 2-(4-methyl)piperidinoethyl, 3-piperidinopropyl or 2-morpholinoethyl group; or (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl group, and the like.

[0040] As a protective group for the carboxyl group, it is preferably a C₁-C₄ alkyl group; benzyl group; a C₁-C₂ alkyl group substituted by a C₂-C₅ alkanoyloxy group; a C₁-C₂ alkyl group substituted by a (C₁-C₄ alkoxy)carbonyloxy group; or (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl group,

[0041] more preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl, acetoxymethyl, 1-acetoxyethyl, pivaloyloxymethyl or 1-pivaloyloxyethyl group.

[0042] In the above-mentioned formula (I), m is an integer of 1 to 4, m is preferably 1, 2 or 3, and particularly preferably 1 or 2. When m is 2 or more, R¹s may be different from each other.

[0043] In the above-mentioned formula (I), n is an integer of 1 to 3, preferably n is 1 or 2, particularly preferably 1. When n is 2 or more, R²s may be different from each other.

[0044] In the Compound (I) of the present invention, there exist an optical isomer(s) (including diastereomer) due to an asymmetric carbon atom(s) in the molecule, or there exist a case in which a geometric isomer due to a double bond exists, and these respective isomers are also included in the present invention.

[0045] Also, the Compound (I) of the present invention can be converted into a pharmaceutically acceptable salt, if necessary. Such a pharmaceutically acceptable salt may be mentioned an acid addition salt of a mineral acid such as hydrochloride, hydrobromide, hydroiodide, sulfate or phosphate; an acid addition salt of an organic acid such as trifluoroacetate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, oxalate, maleate, fumarate, tartarate or citrate; a metal salt of a carboxylic acid such as a sodium salt, a potassium salt, a calcium salt, a magnesium salt, a manganese salt, an iron salt or an aluminum salt; or a salt with an organic base such as an ammonium salt, a triethylamine salt, a guanidine salt, a hydrazine salt, a quinine salt or a cinchonine salt, and the like.

[0046] Incidentally, the Compound (I) of the present invention can also exist as a hydrate.

[0047] In the dibenzocycloheptene compound having the above-mentioned formula (I) of the present invention, it is preferably

[0048] (1). a dibenzocycloheptene compound wherein R¹ of the compound represented by the formula (I) is selected from the group consisting of hydrogen atom, fluorine atom, chlorine atom, bromine atom, hydroxy group, nitro group, a cyano group, carbamoyl group, formyl group, carboxyl group, 1H-tetrazol-5-yl group, methyl group, ethyl group, propyl group, isopropyl group, fluoromethyl group, difluoromethyl group, triflubromethyl group, 2-fluoroethyl group, hydroxymethyl group, 1-hydroxyethyl group, 2-hydroxyethyl group, 1-hydroxy-1-methylethyl group, 1-hydroxypropyl group, 2-hydroxypropyl group, vinyl group, 1-propenyl group, allyl group, 1-butenyl group, 2-butenyl group, 2-methyl-1-propenyl group, ethynyl group, 1-propynyl group, 1-butynyl group, methoxy group, ethoxy group, propoxy group, isopropoxy group, fluoromethoxy group, difluoromethoxy group, trifluoromethoxy group, 2-fluoroethoxy group, methylthio group, ethylthio group, propylthio group, isopropylthio group, methylsulfinyl group, ethylsulfinyl group, propylsulfinyl group, isopropylsulfinyl group, methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group and isopropylsulfonyl group,

[0049] (2). a dibenzocycloheptene compound wherein R¹ of the compound represented by the formula (I) is selected from the group consisting of hydrogen atom, fluorine atom, chlorine atom, hydroxy group, nitro group, cyano group, carbamoyl group, formyl group, 1H-tetrazol-5-yl group, methyl group, ethyl group, fluoromethyl group, difluoromethyl group, trifluoromethyl group, hydroxymethyl group, 1-hydroxyethyl group, 1-hydroxy-1-methylethyl group, 1-hydroxypropyl group, vinyl group, 1-propenyl group, allyl group, ethynyl group, 1-propynyl group, 1-butynyl group, methoxy group, ethoxy group, fluoromethoxy group, difluoromethoxy group, trifluoromethoxy group, methylthio group, ethylthio group, methylsulfinyl group, ethylsulfinyl group, methylsulfonyl group and ethylsulfonyl group,

[0050] (3). a dibenzocycloheptene compound wherein R¹ of the compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a nitro group, a cyano group, a formyl group, 1H-tetrazol-5-yl group, methyl group, difluoromethyl group, trifluoromethyl group, hydroxymethyl group, 1hydroxy-1-methylethyl group, vinyl group, ethynyl group, methoxy group, difluoromethoxy group, trifluoromethoxy group, methylthio group, methylsulfinyl group and methylsulfonyl group,

[0051] (4). a dibenzocycloheptene compound wherein R¹ of the compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a cyano group, trifluoromethyl group, hydroxymethyl group, 1-hydroxy-1-methylethyl group, ethynyl group, methoxy group, difluoromethoxy group, trifluoromethoxy group, methylsulfinyl group and methylsulfonyl group,

[0052] (5). a dibenzocycloheptene compound wherein R² of the compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, bromine atom, a nitro group, a cyano group, methyl group, ethyl group, propyl group, isopropyl group, methoxy group, ethoxy group, propoxy group and isopropoxy group,

[0053] (6). a dibenzocycloheptene compound wherein R² of the compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a nitro group, a cyano group, methyl group, ethyl group, methoxy group and ethoxy group,

[0054] (7). a dibenzocycloheptene compound wherein R² of the compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, methyl group and methoxy group,

[0055] (8). a dibenzocycloheptene compound wherein R² of the compound represented by the formula (I) is a hydrogen atom,

[0056] (9). a dibenzocycloheptene compound wherein A of the compound represented by the formula (I) is selected from the group consisting of 2-thiazolyl, 1,3,4-thiadiazol-2-yl, 2-pyridyl, 2-pyrimidinyl, 2-benzoxazolyl, 2-benzothiazolyl, quinolin-2-yl, quinazolin-2-yl, 4-methyl-2-thiazolyl, 4-isopropyl-2-thiazolyl, 4-t-butyl-2-thiazolyl, 4-trifluoromethyl-2-thiazolyl, 5-methyl-1,3,4-thiadiazol-2-yl, 5-isopropyl-1,3,4-thiadiazol-2-yl, 5-t-butyl-1,3,4-thiadiazol-2-yl, 5-trifluoromethyl-1,3,4-thiadiazol-2-yl, 5,6-difluoro-2-pyridyl, 5,6-dichloro-2-pyridyl, 5,6-dimethyl-2-pyridyl, 5H-6,7-dihydrocyclopenta[b]pyridin-2-yl, 5,6,7,8-tetrahydroquinolin-2-yl, 5,6-difluoro-2-pyrimidinyl, 5,6-dichloro-2-pyrimidinyl, 5,6-dimethyl-2-pyrimidinyl, 6-trifluoromethyl-2-pyrimidinyl, 5H-6,7-dihydrocyclopenta[d]pyrimidin-2-yl, 5,6,7,8-tetrahydroquinazolin-2-yl, 6-fluoro-2-benzoxazolyl, 5-fluoro-2-benzoxazolyl, 5,6-difluoro-2-benzoxazolyl, 6-chloro-2-benzoxazolyl, 5-chloro2-benzoxazolyl, 5,6-dichloro-2-benzoxazolyl, 5-chloro-6-fluoro-2-benzoxazolyl, 5-methyl-2-benzoxazolyl, 5-cyano-2-benzoxazolyl, 5-trifluoromethyl-2-benzoxazolyl, 5-methylthio-2-benzoxazolyl, 6-fluoro-2-benzothiazolyl, 5-fluoro-2-benzothiazolyl, 5,6-difluoro-2-benzothiazolyl, 6-chloro-2-benzothiazolyl, 5-chloro-2-benzothiazolyl, 5,6-dichloro-2-benzothiazolyl, 5-chloro-6-fluoro-2-benzothiazolyl, 5-methyl-2-benzothiazolyl, 5-cyano-2-benzothiazolyl, 5-trifluoromethyl-2-benzothiazolyl, 5-methylthio-2-benzothiazolyl, 5-fluoroquinolin-2-yl, 6-fluoroquinolin-2-yl, 7-fluoroquinolin-2-yl, 5-chloroquinolin-2-yl, 6-chloroquinolin-2-yl, 7-chloroquinolin-2-yl, 7-methylquinolin-2-yl, 7-trifluoromethylquinolin-2-yl, 7-methoxyquinolin-2-yl, 7-difluoromethoxyquinolin-2-yl, 7-trifluoromethoxyquinolin-2-yl, 5,7-difluoroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 5,7-dichloroquinolin-2-yl, 6,7-dichloroquinolin-2-yl, 5-chloro-7-fluoroquinolin-2-yl, 6-chloro-7-fluoroquinolin-2-yl, 7-chloro-5-fluoroquinolin-2-yl, 7-chloro-6-fluoroquinolin-2-yl, 7-chloro-6-cyanoquinolin-2-yl, 7-cyano-6-fluoroquinolin-2-yl, 6-fluoro-7-trifluoromethylquinolin-2-yl, 5,6,7-trifluoroquinolin-2-yl, 5-fluoroquinazolin-2-yl, 6-fluoroquinazolin-2-yl, 7-fluoroquinazolin-2-yl, 5-chloroquinazolin-2-yl, 6-chloroquinazolin-2-yl, 7-chloroquinazolin-2-yl, 7-methylquinazolin-2-yl, 7-trifluoromethylquinazolin-2-yl, 7-methoxyquinazolin-2-yl, 7-difluoromethoxyquinazolin-2-yl, 7-trifluoromethoxyquinazolin-2-yl, 5,7-difluoroquinazolin-2-yl, 6,7-difluoroquinazolin-2-yl, 5,7-dichloroquinazolin-2-yl, 6,7-dichloroquinazolin-2-yl, 5-chloro-7-fluoroquinazolin-2-yl, 6-chloro-7-fluoroquinazolin-2-yl, 7-chloro-5-fluoroquinazolin-2-yl, 7-chloro-6-fluoroquinazolin-2-yl, 7-chloro-6-cyanoquinazolin-2-yl, 7-cyano-6-fluoroquinazolin-2-yl, 6-fluoro-7-trifluoromethylquinazolin-2-yl and 5,6,7-trifluoroquinazolin-2-yl group,

[0057] (10). a dibenzocycloheptene compound wherein A of the compound represented by the formula (I) is selected from the group consisting of 2-pyridyl, 2-benzothiazolyl, quinolin-2-yl, 5,6-difluoro-2-pyridyl, 5,6-dichloro-2-pyridyl, 5,6-dimethyl-2-pyridyl, 5,6,7,8-tetrahydroquinolin-2-yl, 6-fluoro-2-benzothiazolyl, 5-fluoro-2-benzothiazolyl, 5,6-difluoro-2-benzothiazolyl, 6-chloro-2-benzothiazolyl, 5-chloro-2-benzothiazolyl, 5,6-dichloro-2-benzothiazolyl, 5-chloro-6-fluoro-2-benzothiazolyl, 5-methyl-2-benzothiazolyl, 5-cyano-2-benzothiazolyl, 5-trifluoromethyl-2-benzothiazolyl, 5-methylthio-2-benzothiazolyl, 5-fluoroquinolin-2-yl, 6-fluoroquinolin-2-yl, 7-fluoroquinolin-2-yl, 5-chloroquinolin-2-yl, 6-chloroquinolin-2-yl, 7-chloroquinolin-2-yl, 7-methylquinolin-2-yl, 7-trifluoromethylquinolin-2-yl, 7-methoxyquinolin-2-yl, 7-difluoromethoxyquinolin-2-yl, 7-trifluoromethoxyquinolin-2-yl, 5,7-difluoroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 5,7-dichloroquinolin-2-yl, 6,7-dichloroquinolin-2-yl, 5-chloro-7-fluoroquinolin-2-yl, 6-chloro-7-fluoroquinolin-2-yl, 7-chloro-5-fluoroquinolin-2-yl, 7-chloro-6-fluoroquinolin-2-yl, 7-chloro-6-cyanoquinolin-2-yl, 7-cyano-6-fluoroquinolin-2-yl, 6-fluoro-7-trifluoromethylquinolin-2-yl and 5,6,7-trifluoroquinolin-2-yl group,

[0058] (11). a dibenzocycloheptene compound wherein A of the compound represented by the formula (I) is selected from the group consisting of 5,6,7,8-tetrahydroquinolin-2-yl, 7-fluoroquinolin-2-yl, 7-chloroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 6,7-dichloroquinolin-2-yl and 7-chloro-6-fluoroquinolin-2-yl group,

[0059] (12). a dibenzocycloheptene compound wherein B of the compound represented by the formula (I) is a formula: —CH═CH—, a formula: —OCH₂— or a formula: —CH₂O—,

[0060] (13). a dibenzocycloheptene compound wherein X of the compound represented by the formula (I) is an oxygen atom or a sulfur atom,

[0061] (14). a dibenzocycloheptene compound wherein Y of the compound represented by the formula (I) is selected from the group consisting of methylene, ethylene, trimethylene, tetramethylene, pentamethylene, fluoromethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, ethylidene, 1-methylethylene, 2-methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethylene, 1-methoxyethylene, 2-methoxyethylene, 1-fluorotrimethylene, 2-fluorotrimethylene, 3-fluorotrimethylene, 1,1-difluorotrimethylene, 2,2-difluorotrimethylene, 3,3-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, 2,2-diethyltrimethylene, 2-methoxytrimethylene, 3-methoxytrimethylene, 2,2-dimethoxytrimethylene, 3,3-dimethoxytrimethylene, (a-1) group, (a-2) group, (a-3) group, (a-4) group, (a-5) group and (a-6) group,

[0062] (15). a dibenzocycloheptene compound wherein Y of the compound represented by the formula (I) is selected from the group consisting of methylene, ethylene, trimethylene, fluoromethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, ethylidene, 1-methylethylene, 2-methylethylene, 1-fluorotrimethylene, 2-fluorotrimethylene, 3-fluorotrimethylene, 1,1-difluorotrimethylene, 2,2-difluorotrimethylene, 3,3-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, (a-4) group, (a-5) group and (a-6) group,

[0063] (16). a dibenzocycloheptene compound wherein Y of the compound represented by the formula (I) is selected from the group consisting of methylene, ethylene, trimethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, ethylidene, 1-methylethylene, 2-methylethylene, 2,2-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene and (a-5) group,

[0064] (17). a dibenzocycloheptene compound wherein Y of the compound represented by the formula (I) is selected from the group consisting of methylene, ethylene, trimethylene, ethylidene, 1-methylethylene, 2-methylethylene and (a-5) group,

[0065] (18). a dibenzocycloheptene compound wherein Z of the compound represented by the formula (I) is selected from the group consisting of carboxy, 1H-tetrazol-5-yl, methanesulfonylamino, ethanesulfonylamino, trifluoromethanesulfonylamino, phenylsulfonylamino, p-fluorophenylsulfonylamino, p-chlorophenylsulfonylamino, o-methylphenylsulfonylamino, p-methylphenylsulfonylamino, p-trifluoromethylphenylsulfonylamino, o-methoxyphenylsulfonylamino, p-methoxyphenylsulfonylamino, p-difluoromethoxyphenylsulfonylamino, p-trifluoromethoxyphenylsulfonylamino, p-nitrophenylsulfonylamino, p-cyanophenylsulfonylamino, methanesulfonylaminocarbonyl, ethanesulfonylaminocarbonyl, trifluoromethanesulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, p-fluorophenylsulfonylaminocarbonyl, p-chlorophenylsulfonylaminocarbonyl, o-methylphenylsulfonylaminocarbonyl, p-methylphenylsulfonylaminocarbonyl, p-trifluoromethylphenylsulfonylaminocarbonyl, o-methoxyphenylsulfonylaminocarbonyl, p-methoxyphenylsulfonylaminocarbonyl, p-difluoromethoxyphenylsulfonylaminocarbonyl, p-trifluoromethoxyphenylsulfonylaminocarbonyl, p-nitrophenylsulfonylaminocarbonyl and p-cyanophenylsulfonylaminocarbonyl group,

[0066] (19). a dibenzocycloheptene compound wherein Z of the compound represented by the formula (I) is selected from the group consisting of carboxy, 1H-tetrazol-5-yl, methanesulfonylamino, trifluoromethanesulfonylamino, phenylsulfonylamino, o-methylphenylsulfonylamino, p-methylphenylsulfonylamino, methanesulfonylaminocarbonyl, trifluoromethanesulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, o-methylphenylsulfonylaminocarbonyl and p-methylphenylsulfonylaminocarbonyl group,

[0067] (20). a dibenzocycloheptene compound wherein Z of the compound represented by the formula (I) is selected from the group consisting of carboxy, methanesulfonylamino, trifluoromethanesulfonylamino, methanesulfonylaminocarbonyl and trifluoromethanesulfonylaminocarbonyl group,

[0068] (21). a dibenzocycloheptene compound wherein Z of the compound represented by the formula (I) is carboxyl group,

[0069] (22). a dibenzocycloheptene compound wherein when Z of the compound represented by the formula (I) is carboxyl group, the protective group is selected from the group consisting of C₁-C₄ alkyl group; benzyl group; C₁-C₂ alkyl group substituted by C₂-C₅ alkanoyloxy group; C₁-C₂ alkyl group substituted by (C₁-C₄ alkoxy)carbonyloxy group; and (5-methyl-2-oxo-1, 3-dioxolen-4-yl)methyl group,

[0070] (23). a dibenzocycloheptene compound wherein when Z of the compound represented by the formula (I) is carboxyl group, the protective group is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, acetoxymethyl, 1-acetoxyethyl, pivaloyloxymethyl and 1-pivaloyloxyethyl group,

[0071] (24). a dibenzocycloheptene compound wherein m of the compound represented by the formula (I) is 1, 2 or 3,

[0072] (25). a dibenzocycloheptene compound wherein m of the compound represented by the formula (I) is 1 or 2,

[0073] (26). a dibenzocycloheptene compound wherein n of the compound represented by the formula (I) is 1 or 2,

[0074] (27). a dibenzocycloheptene compound wherein n of the compound represented by the formula (I) is 1, and with respect to R¹, the preferable order is increased in the order of (1) to (4), with respect to R², the preferable order is increased in the order of (5) to (8), with respect to A, the preferable order is increased in the order of (9) to (11), with respect to Y, the preferable order is increased in the order of (14) to (17), with respect to Z, the preferable order is increased in the order of (18) to (21), with respect to the protective group when Z is a carboxyl group, the preferable order is increased in the order of (22) to (23), with respect to m, the preferable order is increased in the order of (24) to (25), and with respect to n, the preferable order is increased in the order of (26) to (27).

[0075] Also, as the dibenzocycloheptene compound having the above-mentioned formula (I), a dibenzocycloheptene compound comprising a combination of two or more of the abovementioned (1) to (27) is preferred.

[0076] For example, the following may be mentioned,

[0077] (28). a compound wherein R¹ of the compound represented by the formula (I) is selected from the group consisting of hydrogen atom, fluorine atom, chlorine atom, nitro group, cyano group, formyl group, 1H-tetrazol-5-yl group, methyl group, difluoromethyl group, trifluoromethyl group, hydroxymethyl group, 1-hydroxy-1-methylethyl group, vinyl group, ethynyl group, methoxy group, difluoromethoxy group, trifluoromethoxy group, methylthio group, methylsulfinyl group and methylsulfonyl group, R² is selected from the group consisting of hydrogen atom, fluorine atom, chlorine atom, methyl group and methoxy group, A is selected from the group consisting of 5,6,7,8-tetrahydroquinolin-2-yl, 7-fluoroquinolin-2-yl, 7-chloroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 6,7-dichloroquinolin-2-yl and 7-chloro-6-fluoroquinolin-2-yl group, B is a formula: —CH═CH—, a formula: —OCH₂— or a formula: —CH₂O—, X is selected from the group consisting of an oxygen atom or a sulfur atom, Y is selected from the group consisting of methylene, ethylene, trimethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, ethylidene, 1-methylethylene, 2-methylethylene, 2,2-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene and (a-5) group, Z is selected from the group consisting of carboxy, methanesulfonylamino, trifluoromethanesulfonylamino, methanesulfonylaminocarbonyl and trifluoromethanesulfonylaminocarbonyl group, m is 1 or 2, and n is 1.

[0078] (29). a compound wherein R¹ of the compound represented by the formula (I) is selected from the group consisting of hydrogen atom, fluorine atom, chlorine atom, cyano group, trifluoromethyl group, hydroxymethyl group, 1-hydroxy-1-methylethyl group, ethynyl group, methoxy group, difluoromethoxy group, trifluoromethoxy group, methylsulfinyl group and methylsulfonyl group, R² is a hydrogen atom, A is selected from the group consisting of 5,6,7,8-tetrahydroquinolin-2-yl, 7-fluoroquinolin-2-yl, 7-chloroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 6,7-dichloroquinolin-2-yl and 7-chloro-6-fluoroquinolin-2-yl group, B is a formula: —CH═CH—, a formula: —OCH₂— or a formula: —CH₂O—, X is an oxygen atom or a sulfur atom, Y is selected from the group consisting of methylene, ethylene, trimethylene, ethylidene, 1-methylethylene, 2-methylethylene and (a-5) group, Z is carboxy group, m is 1 or 2, and n is 1.

[0079] As preferred compounds in the compound (I), compounds in the following Table 1 can be specifically exemplified. TABLE 1 (I)

No. A B (R²)n (R¹)m X—Y—Z 1 6,7-diF-Q —CH═CH— H H —OCH₂COOH 2 6,7-diF-Q —CH═CH— H H —OCH(CH₃)COOH 3 6,7-diF-Q —CH═CH— H H —OCH₂CH₂COOH 4 6,7-diF-Q —CH═CH— H H —OCH₂CH(CH₃)COOH 5 6,7-diF-Q —CH═CH— H H —OCH₂C(CH₂CH₂)CH₂COOH 6 6,7-diF-Q —CH═CH— H H —SCH₂COOH 7 6,7-diF-Q —CH═CH— H H —SCH(CH₃)COOH 8 6,7-diF-Q —CH═CH— H H —SCH₂CH₂COOH 9 6,7-diF-Q —CH═CH— H H —SCH₂CH(CH₃)COOH 10 6,7-diF-Q —CH═CH— H H —SCH₂C(CH₃)₂COOH 11 6,7-diF-Q —CH═CH— H H —SCH₂CH(CH₂CH₃)COOH 12 6,7-diF-Q —CH═CH— H H —SCH(CH₃)CH₂COOH 13 6,7-diF-Q —CH═CH— H H —SC(CH₃)₂CH₂COOH 14 6,7-diF-Q —CH═CH— H H —SCH₂CH₂CH₂COOH 15 6,7-diF-Q —CH═CH— H H —SCH₂CH(CH₃)CH₂COOH 16 6,7-diF-Q —CH═CH— H H —SCH₂C(CH₃)₂CH₂COOH 17 6,7-diF-Q —CH═CH— H H —SCH₂C(CH₂CH₂)CH₂COOH 18 6,7-diF-Q —CH═CH— H H —SCH₂CF₂COOH 19 6,7-diF-Q —CH═CH— H H —SCH₂CF₂CH₂COOH 20 6,7-diF-Q —CH═CH— H H —SCH₂-Tet 21 6,7-diF-Q —CH═CH— H H —SCH₂CH₂-Tet 22 6,7-diF-Q —CH═CH— H H —SCH₂NHSO₂CF₃ 23 6,7-diF-Q —CH═CH— H H —SCH₂CONHSO₂CH₃ 24 6,7-diF-Q —CH═CH— H H —SCH₂CONHSO₂CF₃ 25 6,7-diF-Q —CH═CH— H H —SCH₂CONHSO₂Ph 26 6,7-diF-Q —CH═CH— H H —SCH₂CONHSO₂(2-CH₃—Ph) 27 6,7-diF-Q —CH═CH— H H —SCH₂CH₂NHSO₂CF₃ 28 6,7-diF-Q —CH═CH— H H —SCH₂CH₂CONHSO₂CH₃ 29 6,7-diF-Q —CH═CH— H H —SCH₂CH₂CONHSO₂CF₃ 30 6,7-diF-Q —CH═CH— H H —SCH₂CH₂CONHSO₂Ph 31 6,7-diF-Q —CH═CH— H H —SCH₂CH₂CONHSO₂(2-CH₃—Ph) 32 6,7-diF-Q —CH═CH— H H —CH₂COOH 33 6,7-diF-Q —CH═CH— H H —CH₂CH₂COOH 34 6,7-diF-Q —CH═CH— H H —CH₂CH₂CH₂COOH 35 6,7-diF-Q —CH═CH— H 9-F —OCH₂COOH 36 6,7-diF-Q —CH═CH— H 9-F —OCH(CH₃)COOH 37 6,7-diF-Q —CH═CH— H 9-F —OCH₂CH₂COOH 38 6,7-diF-Q —CH═CH— H 9-F —SCH₂COOH 39 6,7-diF-Q —CH═CH— H 9-F —SCH(CH₂)COOH 40 6,7-diF-Q —CH═CH— H 9-F —SCH₂CH₂COOH 41 6,7-diF-Q —CH═CH— H 9-F —SCH₂CH(CH₃)COOH 42 6,7-diF-Q —CH═CH— H 9-F —SCH₂CH(CH₂CH₃)COOH 43 6,7-diF-Q —CH═CH— H 9-F —SCH₂C(CH₂CH₂)CH₂COOH 44 6,7-diF-Q —CH═CH— H 8-F —OCH₂COOH 45 6,7-diF-Q —CH═CH— H 8-F —OCH₂CH₂COOH 46 6,7-diF-Q —CH═CH— H 8-F —SCH₂COOH 47 6,7-diF-Q —CH═CH— H 8-F —SCH₂CH₂COOH 48 6,7-diF-Q —CH═CH— H 8-F —SCH₂CH(CH₃)COOH 49 6,7-diF-Q —CH═CH— H 8-F —SCH₂C(CH₂CH₂)CH₂COOH 50 6,7-diF-Q —CH═CH— H 7-F —OCH₂COOH 51 6,7-diF-Q —CH═CH— H 7-F —OCH₂CH₂COOH 52 6,7-diF-Q —CH═CH— H 7-F —SCH₂COOH 53 6,7-diF-Q —CH═CH— H 7-F —SCH₂CH₂COOH 54 6,7-diF-Q —CH═CH— H 7-F —SCH₂CH(CH₃)COOH 55 6,7-diF-Q —CH═CH— H 6-F —OCH₂COOH 56 6,7-diF-Q —CH═CH— H 6-F —OCH(CH₃)COOH 57 6,7-diF-Q —CH═CH— H 6-F —OCH₂CH₂COOH 58 6,7-diF-Q —CH═CH— H 6-F —OCH₂CH(CH3)COOH 59 6,7-diF-Q —CH═CH— H 6-F —OCH₂C(CH₂CH₂)CH₂COOH 60 6,7-diF-Q —CH═CH— H 6-F —SCH₂COOH 61 6,7-diF-Q —CH═CH— H 6-F —SCH(CH₃)COOH 62 6,7-diF-Q —CH═CH— H 6-F —SCH₂CH₂COOH 63 6,7-diF-Q —CH═CH— H 6-F —SCH₂CH(CH₃)COOH 64 6,7-diF-Q —CH═CH— H 6-F —SCH₂C(CH₂CH₂)CH₂COOH 65 6,7-diF-Q —CH═CH— H 9-Cl —OCH₂COOH 66 6,7-diF-Q —CH═CH— H 9-Cl —OCH(CH₃)COOH 67 6,7-diF-Q —CH═CH— H 9-Cl —OCH₂CH₂COOH 68 6,7-diF-Q —CH═CH— H 9-Cl —OCH₂CH(CH3)COOH 69 6,7-diF-Q —CH═CH— H 9-Cl —OCH₂C(CH₂CH₂)CH₂COOH 70 6,7-diF-Q —CH═CH— H 9-Cl —SCH₂COOH 71 6,7-diF-Q —CH═CH— H 9-Cl —SCH(CH₃)COOH 72 6,7-diF-Q —CH═CH— H 9-Cl —SCH₂CH₂COOH 73 6,7-diF-Q —CH═CH— H 9-Cl —SCH₂CH(CH₃)COOH 74 6,7-diF-Q —CH═CH— H 9-Cl —SCH₂C(CH₂CH₂)CH₂COOH 75 6,7-diF-Q —CH═CH— H 8-Cl —SCH₂C(CH₂CH₂)CH₂COOH 76 6,7-diF-Q —CH═CH— H 8-Cl —OCH₂COOH 77 6,7-diF-Q —CH═CH— H 8-Cl —OCH₂CH₂COOH 78 6,7-diF-Q —CH═CH— H 8-Cl —SCH₂COOH 79 6,7-diF-Q —CH═CH— H 8-Cl —SCH₂CH₂COOH 80 6,7-diF-Q —CH═CH— H 8-Cl —SCH₂CH(CH₃)COOH 81 6,7-diF-Q —CH═CH— H 7-Cl —SCH₂C(CH₂CH₂)CH₂COOH 82 6,7-diF-Q —CH═CH— H 7-Cl —OCH₂COOH 83 6,7-diF-Q —CH═CH— H 7-Cl —OCH₂CH₂COOH 84 6,7-diF-Q —CH═CH— H 7-Cl —SCH₂COOH 85 6,7-diF-Q —CH═CH— H 7-Cl —SCH₂CH₂COOH 86 6,7-diF-Q —CH═CH— H 7-Cl —SCH₂CH(CH₃)COOH 87 6,7-diF-Q —CH═CH— H 6-Cl —OCH₂COOH 88 6,7-diF-Q —CH═OH— H 6-Cl —OCH(CH₃)COOH 89 6,7-diF-Q —CH═CH— H 6-Cl —OCH₂CH₂COOH 90 6,7-diF-Q —CH═CH— H 6-Cl —OCH₂CH(CH3)COOH 91 6,7-diF-Q —CH═CH— H 6-Cl —OCH₂C(CH₂CH₂)CH₂COOH 92 6,7-diF-Q —CH═CH— H 6-Cl —SCH₂COOH 93 6,7-diF-Q —CH═CH— H 6-Cl —SCH(CH₃)COOH 94 6,7-diF-Q —CH═OH— H 6-Cl —SCH₂CH₂COOH 95 6,7-diF-Q —CH═CH— H 6-Cl —SCH₂CH(CH₃)COOH 96 6,7-diF-Q —CH═CH— H 6-Cl —SCH₂C(CH₂CH₂)CH₂COOH 97 6,7-diF-Q —CH═CH— H 9-CN —OCH₂COOH 98 6,7-diF-Q —CH═CH— H 9-CN —OCH(CH₃)COOH 99 6,7-diF-Q —CH═CH— H 9-CN —OCH₂CH₂COOH 100 6,7-diF-Q —CH═CH— H 9-CN —OCH₂CH(CH3)COOH 101 6,7-diF-Q —CH═CH— H 9-CN —OCH₂C(CH₂CH₂)CH₂COOH 102 6,7-diF-Q —CH═CH— H 9-CN —SCH₂COOH 103 6,7-diF-Q —CH═CH— H 9-CN —SCH(CH₃)COOH 104 6,7-diF-Q —CH═CH— H 9-CN —SCH₂CH₂COOH 105 6,7-diF-Q —CH═CH— H 9-CN —SCH₂CH(CH₃)COOH 106 6,7-diF-Q —CH═CH— H 9-CN —SCH₂C(CH₂CH₂)CH₂COOH 107 6,7-diF-Q —CH═CH— H 8-CN —OCH₂COOH 108 6,7-diF-Q —CH═CH— H 8-CN —OCH₂CH₂COOH 109 6,7-diF-Q —CH═CH— H 8-CN —SCH₂COOH 110 6,7-diF-Q —CH═CH— H 8-CN —SCH₂CH₂COOH 111 6,7-diF-Q —CH═CH— H 8-CN —SCH₂CH(CH₃)COOH 112 6,7-diF-Q —CH═CH— H 8-CN —SCH₂C(CH₂CH₂)CH₂COOH 113 6,7-diF-Q —CH═CH— H 7-CN —OCH₂COOH 114 6,7-diF-Q —CH═CH— H 7-CN —OCH₂CH₂COOH 115 6,7-diF-Q —CH═CH— H 7-CN —SCH₂COOH 116 6,7-diF-Q —CH═CH— H 7-CN —SCH₂CH₂COOH 117 6,7-diF-Q —CH═CH— H 7-CN —SCH₂CH(CH₃)COOH 118 6,7-diF-Q —CH═CH— H 9-CH₃ —OCH₂COOH 119 6,7-diF-Q —CH═CH— H 9-CH₃ —OCH₂CH₂COOH 120 6,7-diF-Q —CH═CH— H 9-CH₃ —SCH₂COOH 121 6,7-diF-Q —CH═CH— H 9-CH₃ —SCH₂CH₂COOH 122 6,7-diF-Q —CH═CH— H 9-CH₃ —SCH₂CH(CH₃)COOH 123 6,7-diF-Q —CH═CH— H 9-CH₃ —SCH₂CH(CH₂CH₃)COOH 124 6,7-diF-Q —CH═CH— H 9-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 125 6,7-diF-Q —CH═CH— H 8-CH₃ —OCH₂COOH 126 6,7-diF-Q —CH═CH— H 8-CH₃ —OCH₂CH₂COOH 127 6,7-diF-Q —CH═CH— H 8-CH₃ —SCH₂COOH 128 6,7-diF-Q —CH═CH— H 8-CH₃ —SCH₂CH₂COOH 129 6,7-diF-Q —CH═CH— H 8-CH₃ —SCH₂CH(CH₃)COOH 130 6,7-diF-Q —CH═CH— H 8-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 131 6,7-diF-Q —CH═CH— H 7-CH₃ —OCH₂COOH 132 6,7-diF-Q —CH═CH— H 7-CH₃ —OCH₂CH₂COOH 133 6,7-diF-Q —CH═CH— H 7-CH₃ —SCH₂COOH 134 6,7-diF-Q —CH═CH— H 7-CH₃ —SCH₂CH₂COOH 135 6,7-diF-Q —CH═CH— H 7-CH₃ —SCH₂CH(CH₃)COOH 136 6,7-diF-Q —CH═CH— H 9-CF₃ —OCH₂COOH 137 6,7-diF-Q —CH═CH— H 9-CF₃ —OCH(CH₃)COOH 138 6,7-diF-Q —CH═CH— H 9-CF₃ —OCH₂CH₂COOH 139 6,7-diF-Q —CH═CH— H 9-CF₃ —OCH₂CH(CH3)COOH 140 6,7-diF-Q —CH═CH— H 9-CF₃ —OCH₂C(CH₂CH₂)CH₂COOH 141 6,7-diF-Q —CH═CH— H 9-CF₃ —SCH₂COOH 142 6,7-diF-Q —CH═CH— H 9-CF₃ —SCH(CH₃)COOH 143 6,7-diF-Q —CH═CH— H 9-CF₃ —SCH₂CH₂COOH 144 6,7-diF-Q —CH═CH— H 9-CF₃ —SCH₂CH(CH₃)COOH 145 6,7-diF-Q —CH═CH— H 9-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 146 6,7-diF-Q —CH═CH— H 8-CF₃ —OCH₂COOH 147 6,7-diF-Q —CH═CH— H 8-CF₃ —OCH₂CH₂COOH 148 6,7-diF-Q —CH═CH— H 8-CF₃ —SCH₂COOH 149 6,7-diF-Q —CH═CH— H 8-CF₃ —SCH₂CH₂COOH 150 6,7-diF-Q —CH═CH— H 8-CF₃ —SCH₂CH(CH₃)COOH 151 6,7-diF-Q —CH═CH— H 8-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 152 6,7-diF-Q —CH═CH— H 7-CF₃ —OCH₂COOH 153 6,7-diF-Q —CH═CH— H 7-CF₃ —OCH₂CH₂COOH 154 6,7-diF-Q —CH═CH— H 7-CF₃ —SCH₂COOH 155 6,7-diF-Q —CH═CH— H 7-CF₃ —SCH₂CH₂COOH 156 6,7-diF-Q —CH═CH— H 7-CF₃ —SCH₂CH(CH₃)COOH 157 6,7-diF-Q —CH═CH— H 9-C≡CH —OCH₂COOH 158 6,7-diF-Q —CH═CH— H 9-C≡CH —OCH(CH₃)COOH 159 6,7-diF-Q —CH═CH— H 9-C≡CH —OCH₂CH₂COOH 160 6,7-diF-Q —CH═CH— H 9-C≡CH —OCH₂CH(CH3)COOH 161 6,7-diF-Q —CH═CH— H 9-C≡CH —OCH₂C(CH₂CH₂)CH₂COOH 162 6,7-diF-Q —CH═CH— H 9-C≡CH —SCH₂COOH 163 6,7-diF-Q —CH═CH— H 9-C≡CH —SCH(CH₃)COOH 164 6,7-diF-Q —CH═CH— H 9-C≡CH —SCH₂CH₂COOH 165 6,7-diF-Q —CH═CH— H 9-C≡CH —SCH₂CH(CH₃)COOH 166 6,7-diF-Q —CH═CH— H 9-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 167 6,7-diF-Q —CH═CH— H 8-C≡CH —OCH₂COOH 168 6,7-diF-Q —CH═CH— H 8-C≡CH —OCH₂CH₂COOH 169 6,7-diF-Q —CH═CH— H 8-C≡CH —SCH₂COOH 170 6,7-diF-Q —CH═CH— H 8-C≡CH —SCH₂CH₂COOH 171 6,7-diF-Q —CH═CH— H 8-C≡CH —SCH₂CH(CH₃)COOH 172 6,7-diF-Q —CH═CH— H 8-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 173 6,7-diF-Q —CH═CH— H 7-C≡CH —OCH₂COOH 174 6,7-diF-Q —CH═CH— H 7-C≡CH —OCH₂CH₂COOH 175 6,7-diF-Q —CH═CH— H 7-C≡CH —SCH₂COOH 176 6,7-diF-Q —CH═CH— H 7-C≡CH —SCH₂CH₂COOH 177 6,7-diF-Q —CH═CH— H 7-C≡CH —SCH₂CH(CH₃)COOH 178 6,7-diF-Q —CH═CH— H 9-CH₂OH —OCH₂COOH 179 6,7-diF-Q —CH═CH— H 9-CH₂OH —SCH₂CH₂COOH 180 6,7-diF-Q —CH═CH— H 8-CH₂OH —OCH₂COOH 181 6,7-diF-Q —CH═CH— H 8-CH₂OH —SCH₂CH₂COOH 182 6,7-diF-Q —CH═CH— H 7-CH₂OH —OCH₂COOH 183 6,7-diF-Q —CH═CH— H 7-CH₂OH —SCH₂CH₂COOH 184 6,7-diF-Q —CH═CH— H 9- —OCH₂COOH C(CH₃)₂OH 185 6,7-diF-Q —CH═CH— H 9- —SCH₂CH₂COOH C(CH₃)₂OH 186 6,7-diF-Q —CH═CH— H 8- —OCH₂COOH C(CH₃)₂OH 187 6,7-diF-Q —CH═CH— H 8- —SCH₂CH₂COOH C(CH₃)₂OH 188 6,7-diF-Q —CH═CH— H 7- —OCH₂COOH C(CH₃)₂OH 189 6,7-diF-Q —CH═CH— H 7- —SCH₂CH₂COOH C(CH₃)₂OH 190 6,7-diF-Q —CH═CH— H 9-OCH₃ —OCH₂COOH 191 6,7-diF-Q —CH═CH— H 9-OCH₃ —SCH₂CH₂COOH 192 6,7-diF-Q —CH═CH— H 8-OCH₃ —OCH₂COOH 193 6,7-diF-Q —CH═CH— H 8-OCH₃ —SCH₂CH₂COOH 194 6,7-diF-Q —CH═CH— H 7-OCH₃ —OCH₂COOH 195 6,7-diF-Q —CH═CH— H 7-OCH₃ —SCH₂CH₂COOH 196 6,7-diF-Q —CH═CH— H 9-OCHF₂ —OCH₂COOH 197 6,7-diF-Q —CH═CH— H 9-OCHF₂ —SCH₂CH₂COOH 198 6,7-diF-Q —CH═CH— H 8-OCHF₂ —OCH₂COOH 199 6,7-diF-Q —CH═CH— H 8-OCHF₂ —SCH₂CH₂COOH 200 6,7-diF-Q —CH═CH— H 7-OCHF₂ —OCH₂COOH 201 6,7-diF-Q —CH═CH— H 7-OCHF₂ —SCH₂CH₂COOH 202 6,7-diF-Q —CH═CH— H 9-OCF₃ —OCH₂COOH 203 6,7-diF-Q —CH═CH— H 9-OCF₃ —SCH₂CH₂COOH 204 6,7-diF-Q —CH═CH— H 8-OCF₃ —OCH₂COOH 205 6,7-diF-Q —CH═CH— H 8-OCF₃ —SCH₂CH₂COOH 206 6,7-diF-Q —CH═CH— H 7-OCF₃ —OCH₂COOH 207 6,7-diF-Q —CH═CH— H 7-OCF₃ —SCH₂CH₂COOH 208 6,7-diF-Q —CH═CH— H 9-SOCH₃ —OCH₂COOH 209 6,7-diF-Q —CH═CH— H 9-SOCH₃ —SCH₂CH₂COOH 210 6,7-diF-Q —CH═CH— H 8-SOCH₃ —OCH₂COOH 211 6,7-diF-Q —CH═CH— H 8-SOCH₃ —SCH₂CH₂COOH 212 6,7-diF-Q —CH═CH— H 7-SOCH₃ —OCH₂COOH 213 6,7-diF-Q —CH═CH— H 7-SOCH₃ —SCH₂CH₂COOH 214 6,7-diF-Q —CH═CH— H 9-SO₂CH₃ —OCH₂COOH 215 6,7-diF-Q —CH═CH— H 9-SO₂CH₃ —SCH₂CH₂COOH 216 6,7-diF-Q —CH═CH— H 8-SO₂CH₃ —OCH₂COOH 217 6,7-diF-Q —CH═CH— H 8-SO₂CH₃ —SCH₂CH₂COOH 218 6,7-diF-Q —CH═CH— H 7-SO₂CH₃ —OCH₂COOH 219 6,7-diF-Q —CH═CH— H 7-SO₂CH₃ —SCH₂CH₂COOH 220 6,7-diF-Q —CH═CH— H 9-CH═CH₂ —SCH₂CH₂COOH 221 6,7-diF-Q —CH═CH— H 8-CH═CH₂ —SCH₂CH₂COOH 222 6,7-diF-Q —CH═CH— H 7-CH═CH₂ —SCH₂CH₂COOH 223 6,7-diF-Q —CH═CH— H 9-NO₂ —OCH₂COOH 224 6,7-diF-Q —CH═CH— H 9-NO₂ —SCH₂CH₂COOH 225 6,7-diF-Q —CH═CH— H 8-NO₂ —OCH₂COOH 226 6,7-diF-Q —CH═CH— H 8-NO₂ —SCH₂CH₂COOH 227 6,7-diF-Q —CH═CH— H 7-NO₂ —OCH₂COOH 228 6,7-diF-Q —CH═CH— H 7-NO₂ —SCH₂CH₂COOH 229 6,7-diF-Q —CH═CH— 1-F H —SCH₂CH₂COOH 230 6,7-diF-Q —CH═CH— 2-F H —SCH₂CH₂COOH 231 6,7-diF-Q —CH═CH— 1-Cl H —SCH₂CH₂COOH 232 6,7-diF-Q —CH═CH— 2-Cl H —SCH₂CH₂COOH 233 6,7-diF-Q —CH═CH— 1-CH₃ H —SCH₂CH₂COOH 234 6,7-diF-Q —CH═CH— 2-CH₃ H —SCH₂CH₂COOH 235 6,7-diF-Q —CH═CH— 1-OCH₃ H —SCH₂CH₂COOH 236 6,7-diF-Q —CH═CH— 2-OCH₃ H —SCH₂CH₂COOH 237 6,7-diF-Q —CH═CH— 1-NO₂ H —SCH₂CH₂COOH 238 6,7-diF-Q —CH═CH— 2-NO₂ H —SCH₂CH₂COOH 239 6,7-diF-Q —CH═CH— 1-CN H —SCH₂CH₂COOH 240 6,7-diF-Q —CH═CH— 2-CN H —SCH₂CH₂COOH 241 6,7-diF-Q —CH₂O— H H —OCH₂COOH 242 6,7-diF-Q —CH₂O— H H —OCH(CH3)COOH 243 6,7-diF-Q —CH₂O— H H —OCH₂CH₂COOH 244 6,7-diF-Q —CH₂O— H H —OCH₂CH(CH₃)COOH 245 6,7-diF-Q —CH₂O— H H —OCH₂C(CH₂CH₂)CH₂COOH 246 6,7-diF-Q —CH₂O— H H —SCH₂COOH 247 6,7-diF-Q —CH₂O— H H —SCH(CH3)COOH 248 6,7-diF-Q —CH₂O— H H —SCH₂CH₂COOH 249 6,7-diF-Q —CH₂O— H H —SCH₂CH(CH₃)COOH 250 6,7-diF-Q —CH₂O— H H —SCH₂C(CH₃)₂COOH 251 6,7-diF-Q —CH₂O— H H —SCH₂CH(CH₂CH₃)COOH 252 6,7-diF-Q —CH₂O— H H —SCH(CH₃)CH₂COOH 253 6,7-diF-Q —CH₂O— H H —SC(CH₃)₂CH₂COOH 254 6,7-diF-Q —CH₂O— H H —SCH₂CH₂CH₂COOH 255 6,7-diF-Q —CH₂O— H H —SCH₂CH(CH₃)CH₂COOH 256 6,7-diF-Q —CH₂O— H H —SCH₂C(CH₃)₂CH₂COOH 257 6,7-diF-Q —CH₂O— H H —SCH₂C(CH₂CH₂)CH₂COOH 258 6,7-diF-Q —CH₂O— H H —SCH₂CF₂COOH 259 6,7-diF-Q —CH₂O— H H —SCH₂CF₂CH₂COOH 260 6,7-diF-Q —CH₂C— H H —SCH₂-Tet 261 6,7-diF-Q —CH₂O— H H —SCH₂CH₂-Tet 262 6,7-diF-Q —CH₂O— H H —SCH₂NHSO₂CF₃ 263 6,7-diF-Q —CH₂O— H H —SCH₂CONHSO₂CH₃ 264 6,7-diF-Q —CH₂O— H H —SCH₂CONHSO₂CF₃ 265 6,7-diF-Q —CH₂O— H H —SCH₂CONHSO₂Ph 266 6,7-diF-Q —CH₂O— H H —SCH₂CONHSO₂(2-CH₃—Ph) 267 6,7-diF-Q —CH₂O— H H —SCH₂CH₂NHSO₂CF₃ 268 6,7-diF-Q —CH₂O— H H —SCH₂CH₂CONHSO₂CH₃ 269 6,7-diF-Q —CH₂O— H H —SCH₂CH₂CONHSO₂CF₃ 270 6,7-diF-Q —CH₂O— H H —SCH₂CH₂CONHSO₂Ph 271 6,7-diF-Q —CH₂O— H H —SCH₂CH₂CONHSO₂(2-CH₃—Ph) 272 6,7-diF-Q —CH₂O— H H —CH₂COOH 273 6,7-diF-Q —CH₂O— H H —CH₂CH₂COOH 274 6,7-diF-Q —CH₂O— H H —CH₂CH₂CH₂COOH 275 6,7-diF-Q —CH₂O— H 9-F —OCH₂COOH 276 6,7-diF-Q —CH₂O— H 9-F —OCH(CH₃)COOH 277 6,7-diF-Q —CH₂O— H 9-F —OCH₂CH₂COOH 278 6,7-diF-Q —CH₂O— H 9-F —OCH₂CH(CH3)COOH 279 6,7-diF-Q —CH₂O— H 9-F —OCH₂C(CH₂CH₂)CH₂COOH 280 6,7-diF-Q —CH₂O— H 9-F —SCH₂COOH 281 6,7-diF-Q —CH₂O— H 9-F —SCH(CH₃)COOH 282 6,7-diF-Q —CH₂O— H 9-F —SCH₂CH₂COOH 283 6,7-diF-Q —CH₂O— H 9-F —SCH₂CH(CH₃)COOH 284 6,7-diF-Q —CH₂O— H 9-F —SCH₂C(CH₂CH₂)CH₂COOH 285 6,7-diF-Q —CH₂O— H 8-F —OCH₂COOH 286 6,7-diF-Q —CH₂O— H 8-F —OCH₂CH₂COOH 287 6,7-diF-Q —CH₂O— H 8-F —SCH₂COOH 288 6,7-diF-Q —CH₂O— H 8-F —SCH₂CH₂COOH 289 6,7-diF-Q —CH₂O— H 8-F —SCH₂CH(CH₃)COOH 290 6,7-diF-Q —CH₂O— H 8-F —SCH₂C(CH₂CH₂)CH₂COOH 291 6,7-diF-Q —CH₂O— H 7-F —OCH₂COOH 292 6,7-diF-Q —CH₂O— H 7-F —OCH₂CH₂COOH 293 6,7-diF-Q —CH₂O— H 7-F —SCH₂COOH 294 6,7-diF-Q —CH₂O— H 7-F —SCH₂CH₂COOH 295 6,7-diF-Q —CH₂O— H 7-F —SCH₂CH(CH₃)COOH 296 6,7-diF-Q —CH₂O— H 6-F —OCH₂COOH 297 6,7-diF-Q —CH₂O— H 6-F —OCH(CH₃)COOH 298 6,7-diF-Q —CH₂O— H 6-F —OCH₂CH₂COOH 299 6,7-diF-Q —CH₂O— H 6-F —OCH₂CH(CH3)COOH 300 6,7-diF-Q —CH₂O— H 6-F —OCH₂C(CH₂CH₂)CH₂COOH 301 6,7-diF-Q —CH₂O— H 6-F —SCH₂COOH 302 6,7-diF-Q —CH₂O— H 6-F —SCH(CH₃)COOH 303 6,7-diF-Q —CH₂O— H 6-F —SCH₂CH₂COOH 304 6,7-diF-Q —CH₂O— H 6-F —SCH₂CH(CH₃)COOH 305 6,7-diF-Q —CH₂O— H 6-F —SCH₂C(CH₂CH₂)CH₂COOH 306 6,7-diF-Q —CH₂O— H 9-Cl —OCH₂COOH 307 6,7-diF-Q —CH₂O— H 9-Cl —OCH(CH₃)COOH 308 6,7-diF-Q —CH₂Q— H 9-Cl —OCH₂CH₂COOH 309 6,7-diF-Q —CH₂O— H 9-Cl —OCH₂CH(CH3)COOH 310 6,7-diF-Q —CH₂O— H 9-Cl —OCH₂C(CH₂CH₂)CH₂COOH 311 6,7-diF-Q —CH₂O— H 9-Cl —SCH₂COOH 312 6,7-diF-Q —CH₂O— H 9-Cl —SCH(CH₃)COOH 313 6,7-diF-Q —CH₂O— H 9-Cl —SCH₂CH₂COOH 314 6,7-diF-Q —CH₂Q— H 9-Cl —SCH₂CH(CH₃)COOH 315 6,7-diF-Q —CH₂O— H 9-Cl —SCH₂C(CH₂CH₂)CH₂COOH 316 6,7-diF-Q —CH₂O— H 8-Cl —SCH₂C(CH₂CH₂)CH₂COOH 317 6,7-diF-Q —CH₂O— H 8-Cl —OCH₂COOH 318 6,7-diF-Q —CH₂O— H 8-Cl —OCH₂CH₂COOH 319 6,7-diF-Q —CH₂O— H 8-Cl —SCH₂COOH 320 6,7-diF-Q —CH₂O— H 8-Cl —SCH₂CH₂COOH 321 6,7-diF-Q —CH₂O— H 8-Cl —SCH₂CH(CH₃)COOH 322 6,7-diF-Q —CH₂O— H 7-Cl —OCH₂COOH 323 6,7-diF-Q —CH₂O— H 7-Cl —OCH₂CH₂COOH 324 6,7-diF-Q —CH₂O— H 7-Cl —SCH₂COOH 325 6,7-diF-Q —CH₂O— H 7-Cl —SCH₂CH₂COOH 326 6,7-diF-Q —CH₂O— H 7-Cl —SCH₂CH(CH₃)COOH 327 6,7-diF-Q —CH₂O— H 9-CN —OCH₂COOH 328 6,7-diF-Q —CH₂O— H 9-CN —OCH(CH₃)COOH 329 6,7-diF-Q —CH₂O— H 9-CN —OCH₂CH₂COOH 330 6,7-diF-Q —CH₂O— H 9-CN —OCH₂CH(CH₃)COOH 331 6,7-diF-Q —CH₂O— H 9-CN —OCH₂C(CH₂CH₂)CH₂COOH 332 6,7-diF-Q —CH₂O— H 9-CN —SCH₂COOH 333 6,7-diF-Q —CH₂O— H 9-CN —SCH(CH₃)COOH 334 6,7-diF-Q —CH₂O— H 9-CN —SCH₂CH₂COOH 335 6,7-diF-Q —CH₂O— H 9-CN —SCH₂CH(CH₃)COOH 336 6,7-diF-Q —CH₂O— H 9-CN —SCH₂C(CH₂CH₂)CH₂COOH 337 6,7-diF-Q —CH₂O— H 8-CN —OCH₂COOH 338 6,7-diF-Q —CH₂O— H 8-CN —OCH₂CH₂COOH 339 6,7-diF-Q —CH₂O— H 8-CN —SCH₂COOH 340 6,7-diF-Q —CH₂O— H 8-CN —SCH₂CH₂COOH 341 6,7-diF-Q —CH₂O— H 8-CN —SCH₂CH(CH₃)COOH 342 6,7-diF-Q —CH₂O— H 8-CN —SCH₂C(CH₂CH₂)CH₂COOH 343 6,7-diF-Q —CH₂O— H 7-CN —OCH₂COOH 344 6,7-diF-Q —CH₂O— H 7-CN —OCH₂CH₂COOH 345 6,7-diF-Q —CH₂O— H 7-CN —SCH₂COOH 346 6,7-diF-Q —CH₂O— H 7-CN —SCH₂CH₂COOH 347 6,7-diF-Q —CH₂O— H 7-CN —SCH₂CH(CH₃)COOH 348 6,7-diF-Q —CH₂O— H 9-CH₃ —OCH₂COOH 349 6,7-diF-Q —CH₂O— H 9-CH₃ —OCH₂CH₂COOH 350 6,7-diF-Q —CH₂O— H 9-CH₃ —SCH₂COOH 351 6,7-diF-Q —CH₂O— H 9-CH₃ —SCH₂CH₂COOH 352 6,7-diF-Q —CH₂O— H 9-CH₃ —SCH₂CH(CH₃)COOH 353 6,7-diF-Q —CH₂O— H 9-CH₃ —SCH₂CH(CH₂CH₃)COOH 354 6,7-diF-Q —CH₂O— H 9-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 355 6,7-diF-Q —CH₂O— H 8-CH₃ —OCH₂COOH 356 6,7-diF-Q —CH₂O— H 8-CH₃ —OCH₂CH₂COOH 357 6,7-diF-Q —CH₂O— H 8-CH₃ —SCH₂COOH 358 6,7-diF-Q —CH₂O— H 8-CH₃ —SCH₂CH₂COOH 359 6,7-diF-Q —CH₂O— H 8-CH₃ —SCH₂CH(CH₃)COOH 360 6,7-diF-Q —CH₂O— H 8-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 361 6,7-diF-Q —CH₂O— H 7-CH₃ —OCH₂COOH 362 6,7-diF-Q —CH₂O— H 7-CH₃ —OCH₂CH₂COOH 363 6,7-diF-Q —CH₂O— H 7-CH₃ —SCH₂COOH 364 6,7-diF-Q —CH₂O— H 7-CH₃ —SCH₂CH₂COOH 365 6,7-diF-Q —CH₂O— H 7-CH₃ —SCH₂CH(CH₃)COOH 366 6,7-diF-Q —CH₂O— H 9-CF₃ —OCH₂COOH 367 6,7-diF-Q —CH₂O— H 9-CF₃ —OCH(CH₃)COOH 368 6,7-diF-Q —CH₂O— H 9-CF₃ —OCH₂CH₂COOH 369 6,7-diF-Q —CH₂O— H 9-CF₃ —OCH₂CH(CH3)COOH 370 6,7-diF-Q —CH₂O— H 9-CF₃ —OCH₂C(CH₂CH₂)CH₂COOH 371 6,7-diF-Q —CH₂O— H 9-CF₃ —SCH₂COOH 372 6,7-diF-Q —CH₂O— H 9-CF₃ —SCH(CH₃)COOH 373 6,7-diF-Q —CH₂O— H 9-CF₃ —SCH₂CH₂COOH 374 6,7-diF-Q —CH₂O— H 9-CF₃ —SCH₂CH(CH₃)COOH 375 6,7-diF-Q —CH₂O— H 9-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 376 6,7-diF-Q —CH₂O— H 8-CF₃ —OCH₂COOH 377 6,7-diF-Q —CH₂O— H 8-CF₃ —OCH₂CH₂COOH 378 6,7-diF-Q —CH₂O— H 8-CF₃ —SCH₂COOH 379 6,7-diF-Q —CH₂O— H 8-CF₃ —SCH₂CH₂COOH 380 6,7-diF-Q —CH₂O— H 8-CF₃ —SCH₂CH(CH₃)COOH 381 6,7-diF-Q —CH₂O— H 8-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 382 6,7-diF-Q —CH₂O— H 7-CF₃ —OCH₂COOH 383 6,7-diF-Q —CH₂O— H 7-CF₃ —OCH₂CH₂COOH 384 6,7-diF-Q —CH₂O— H 7-CF₃ —SCH₂COOH 385 6,7-diF-Q —CH₂O— H 7-CF₃ —SCH₂CH₂COOH 386 6,7-diF-Q —CH₂O— H 7-CF₃ —SCH₂CH(CH₃)COOH 387 6,7-diF-Q —CH₂O— H 9-C≡CH —OCH₂COOH 388 6,7-diF-Q —CH₂O— H 9-C≡CH —OCH(CH₃)COOH 389 6,7-diF-Q —CH₂O— H 9-C≡CH —OCH₂CH₂COOH 390 6,7-diF-Q —CH₂O— H 9-C≡CH —OCH₂CH(CH₃)COOH 391 6,7-diF-Q —CH₂O— H 9-C≡CH —OCH₂C(CH₂CH₂)CH₂COOH 392 6,7-diF-Q —CH₂O— H 9-C≡CH —SCH₂COOH 393 6,7-diF-Q —CH₂O— H 9-C≡CH —SCH(CH₃)COOH 394 6,7-diF-Q —CH₂O— H 9-C≡CH —SCH₂CH₂COOH 395 6,7-diF-Q —CH₂O— H 9-C≡CH —SCH₂CH(CH₃)COOH 396 6,7-diF-Q —CH₂O— H 9-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 397 6,7-diF-Q —CH₂O— H 8-C≡CH —OCH₂COOH 398 6,7-diF-Q —CH₂O— H 8-C≡CH —OCH₂CH₂COOH 399 6,7-diF-Q —CH₂O— H 8-C≡CH —SCH₂COOH 400 6,7-diF-Q —CH₂O— H 8-C≡CH —SCH₂CH₂COOH 401 6,7-diF-Q —CH₂O— H 8-C≡CH —SCH₂CH(CH₃)COOH 402 6,7-diF-Q —CH₂O— H 8-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 403 6,7-diF-Q —CH₂O— H 7-C≡CH —OCH₂COOH 404 6,7-diF-Q —CH₂O— H 7-C≡CH —OCH₂CH₂COOH 405 6,7-diF-Q —CH₂O— H 7-C≡CH —SCH₂COOH 406 6,7-diF-Q —CH₂O— H 7-C≡CH —SCH₂CH₂COOH 407 6,7-diF-Q —CH₂O— H 7-C≡CH —SCH₂CH(CH₃)COOH 408 6,7-diF-Q —CH₂O— H 9-CH₂OH —OCH₂COOH 409 6,7-diF-Q —CH₂O— H 9-CH₂OH —SCH₂CH₂COOH 410 6,7-diF-Q —CH₂O— H 8-CH₂OH —OCH₂COOH 411 6,7-diF-Q —CH₂O— H 8-CH₂OH —SCH₂CH₂COOH 412 6,7-diF-Q —CH₂O— H 7-CH₂OH —OCH₂COOH 413 6,7-diF-Q —CH₂O— H 7-CH₂OH —SCH₂CH₂COOH 414 6,7-diF-Q —CH₂O— H 9- —OCH₂COOH C(CH₃)₂OH 415 6,7-diF-Q —CH₂O— H 9- —SCH₂CH₂COOH C(CH₃)₂OH 416 6,7-diF-Q —CH₂O— H 8- —OCH₂COOH C(CH₃)₂OH 417 6,7-diF-Q —CH₂O— H 8- —SCH₂CH₂COOH C(CH₃)₂OH 418 6,7-diF-Q —CH₂O— H 7- —OCH₂COOH C(CH₃)₂OH 419 6,7-diF-Q —CH₂O— H 7- —SCH₂CH₂COOH C(CH₃)₂OH 420 6,7-diF-Q —CH₂O— H 9-OCH₃ —OCH₂COOH 421 6,7-diF-Q —CH₂O— H 9-OCH₃ —SCH₂CH₂COOH 422 6,7-diF-Q —CH₂O— H 8-OCH₃ —OCH₂COOH 423 6,7-diF-Q —CH₂O— H 8-OCH₃ —SCH₂CH₂COOH 424 6,7-diF-Q —CH₂O— H 7-OCH₃ —OCH₂COOH 425 6,7-diF-Q —CH₂O— H 7-OCH₃ —SCH₂CH₂COOH 426 6,7-diF-Q —CH₂O— H 9-OCHF₂ —OCH₂COOH 427 6,7-diF-Q —CH₂O— H 9-OCHF₂ —SCH₂CH₂COOH 428 6,7-diF-Q —CH₂O— H 8-OCHF₂ —OCH₂COOH 429 6,7-diF-Q —CH₂O— H 8-OCHF₂ —SCH₂CH₂COOH 430 6,7-diF-Q —CH₂O— H 7-OCHF₂ —OCH₂COOH 431 6,7-diF-Q —CH₂O— H 7-OCHF₂ —SCH₂CH₂COOH 432 6,7-diF-Q —CH₂O— H 9-OCF₃ —OCH₂COOH 433 6,7-diF-Q —CH₂O— H 9-OCF₃ —SCH₂CH₂COOH 434 6,7-diF-Q —CH₂O— H 8-OCF₃ —OCH₂COOH 435 6,7-diF-Q —CH₂O— H 8-OCF₃ —SCH₂CH₂COOH 436 6,7-diF-Q —CH₂O— H 7-OCF₃ —OCH₂COOH 437 6,7-diF-Q —CH₂O— H 7-OCF₃ —SCH₂CH₂COOH 438 6,7-diF-Q —CH₂O— H 9-SOCH₃ —OCH₂COOH 439 6,7-diF-Q —CH₂O— H 9-SOCH₃ —SCH₂CH₂COOH 440 6,7-diF-Q —CH₂O— H 8-SOCH₃ —OCH₂COOH 441 6,7-diF-Q —CH₂O— H 8-SOCH₃ —SCH₂CH₂COOH 442 6,7-diF-Q —CH₂O— H 7-SOCH₃ —OCH₂COOH 443 6,7-diF-Q —CH₂O— H 7-SOCH₃ —SCH₂CH₂COOH 444 6,7-diF-Q —CH₂O— H 9-SO₂CH₃ —OCH₂COOH 445 6,7-diF-Q —CH₂O— H 9-SO₂CH₃ —SCH₂CH₂COOH 446 6,7-diF-Q —CH₂Q— H 8-SO₂CH₃ —OCH₂COOH 447 6,7-diF-Q —CH₂O— H 8-SO₂CH₃ —SCH₂CH₂COOH 448 6,7-diF-Q —CH₂O— H 7-SO₂CH₃ —OCH₂COOH 449 6,7-diF-Q —CH₂O— H 7-SO₂CH₃ —SCH₂CH₂COOH 450 6,7-diF-Q —CH₂O— H 9-CH═CH₂ —SCH₂CH₂COOH 451 6,7-diF-Q —CH₂O— H 8-CH═CH₂ —SCH₂CH₂COOH 452 6,7-diF-Q —CH₂O— H 7-CH═CH₂ —SCH₂CH₂COOH 453 6,7-diF-Q —CH₂O— H 9-NO₂ —OCH₂COOH 454 6,7-diF-Q —CH₂O— H 9-NO₂ —SCH₂CH₂COOH 455 6,7-diF-Q —CH₂O— H 8-NO₂ —OCH₂COOH 456 6,7-diF-Q —CH₂O— H 8-NO₂ —SCH₂CH₂COOH 457 6,7-diF-Q —CH₂O— H 7-NO₂ —OCH₂COOH 458 6,7-diF-Q —CH₂O— H 7-NO₂ —SCH₂CH₂COOH 459 6,7-diF-Q —CH₂O— 1-F H —SCH₂CH₂COOH 460 6,7-diF-Q —CH₂O— 2-F H —SCH₂CH₂COOH 461 6,7-diF-Q —CH₂O— 1-Cl H —SCH₂CH₂COOH 462 6,7-diF-Q —CH₂O— 2-Cl H —SCH₂CH₂COOH 463 6,7-diF-Q —CH₂O— 1-CH₃ H —SCH₂CH₂COOH 464 6,7-diF-Q —CH₂O— 2-CH₃ H —SCH₂CH₂COOH 465 6,7-diF-Q —CH₂O— 1-OCH₃ H —SCH₂CH₂COOH 466 6,7-diF-Q —CH₂O— 2-OCH₃ H —SCH₂CH₂COOH 467 6,7-diF-Q —CH₂O— 1-NO₂ H —SCH₂CH₂COOH 468 6,7-diF-Q —CH₂O— 2-NO₂ H —SCH₂CH₂COOH 469 6,7-diF-Q —CH₂O— 1-CN H —SCH₂CH₂COOH 470 6,7-diF-Q —CH₂O— 2-CN H —SCH₂CH₂COOH 471 7-Cl,6-F-Q —CH═CH— H H —OCH₂COOH 472 7-Cl,6-F-Q —CH═CH— H H —OCH(CH₃)COOH 473 7-Cl,6-F-Q —CH═CH— H H —OCH₂CH₂COOH 474 7-Cl,6-F-Q —CH═CH— H H —OCH₂CH(CH₃)COOH 475 7-Cl,6-F-Q —CH═CH— H H —OCH₂C(CH₂CH₂)CH₂COOH 476 7-Cl,6-F-Q —CH═CH— H H —SCH₂COOH 477 7-Cl,6-F-Q —CH═CH— H H —SCH(CH₃)COOH 478 7-Cl,6-F-Q —CH═CH— H H —SCH₂CH₂COOH 479 7-Cl,6-F-Q —CH═CH— H H —SCH₂CH(CH₃)COOH 480 7-Cl,6-F-Q —CH═CH— H H —SCH₂C(CH₃)₂COOH 481 7-Cl,6-F-Q —CH═CH— H H —SCH₂CH(CH₂CH₃)COOH 482 7-Cl,6-F-Q —CH═CH— H H —SCH(CH₃)CH₂COOH 483 7-Cl,6-F-Q —CH═CH— H H —SO(CH₃)₂CH₂COOH 484 7-Cl,6-F-Q —CH═CH— H H —SCH₂CH₂CH₂COOH 485 7-Cl,6-F-Q —CH═CH— H H —SCH₂CH(CH₃)CH₂COOH 486 7-Cl,6-F-Q —CH═CH— H H —SCH₂C(CH₃)₂CH₂COOH 487 7-Cl,6-F-Q —CH═CH— H H —SCH₂C(CH₂CH₂)CH₂COOH 488 7-Cl,6-F-Q —CH═CH— H H —SCH₂CF₂COOH 489 7-Cl,6-F-Q —CH═CH— H H —SCH₂CF₂CH₂COOH 490 7-Cl,6-F-Q —CH═CH— H H —SCH₂-Tet 491 7-Cl,6-F-Q —CH═CH— H H —SCH₂CH₂-Tet 492 7-Cl,6-F-Q —CH═CH— H H —SCH₂NHSO₂CF₃ 493 7-Cl,6-F-Q —CH═CH— H H —SCH₂CONHSO₂CH₃ 494 7-Cl,6-F-Q —CH═CH— H H —SCH₂CONHSO₂CF₃ 495 7-Cl,6-F-Q —CH═CH— H H —SCH₂CONHSO₂Ph 496 7-Cl,6-F-Q —CH═CH— H H —SCH₂CONHSO₂(2-CH₃—Ph) 497 7-Cl,6-F-Q —CH═CH— H H —SCH₂CH₂NHSO₂CF₃ 498 7-Cl,6-F-Q —CH═CH— H H —SCH₂CH₂CONHSO₂CH₃ 499 7-Cl,6-F-Q —CH═CH— H H —SCH₂CH₂CONHSO₂CF₃ 500 7-Cl,6-F-Q —CH═CH— H H —SCH₂CH₂CONHSO₂Ph 501 7-Cl,6-F-Q —CH═CH— H H —SCH₂CH₂CONHSO₂(2-CH₃—Ph) 502 7-Cl,6-F-Q —CH═CH— H H —CH₂COOH 503 7-Cl,6-F-Q —CH═CH— H H —CH₂CH₂COOH 504 7-Cl,6-F-Q —CH═CH— H H —CH₂CH₂CH₂COOH 505 7-Cl,6-F-Q —CH═CH— H 9-F —OCH₂COOH 506 7-Cl,6-F-Q —CH═CH— H 9-F —OCH(CH₃)COOH 507 7-Cl,6-F-Q —CH═CH— H 9-F —OCH₂CH₂COOH 508 7-Cl,6-F-Q —CH═CH— H 9-F —SCH₂COOH 509 7-Cl,6-F-Q —CH═CH— H 9-F —SCH(CH₃)COOH 510 7-Cl,6-F-Q —CH═CH— H 9-F —SCH₂CH₂COOH 511 7-Cl,6-F-Q —CH═CH— H 9-F —SCH₂CH(CH₃)COOH 512 7-Cl,6-F-Q —CH═CH— H 9-F —SCH₂CH(CH₂CH₃)COOH 513 7-Cl,6-F-Q —CH═CH— H 9-F —SCH₂C(CH₂CH₂)CH₂COOH 514 7-Cl,6-F-Q —CH═CH— H 8-F —OCH₂COOH 515 7-Cl,6-F-Q —CH═CH— H 8-F —OCH₂CH₂COOH 516 7-Cl,6-F-Q —CH═CH— H 8-F —SCH₂COOH 517 7-Cl,6-F-Q —CH═CH— H 8-F —SCH₂CH₂COOH 518 7-Cl,6-F-Q —CH═CH— H 8-F —SCH₂CH(CH₃)COOH 519 7-Cl,6-F-Q —CH═CH— H 8-F —SCH₂C(CH₂CH₂)CH₂COOH 520 7-Cl,6-F-Q —CH═CH— H 7-F —OCH₂COOH 521 7-Cl,6-F-Q —CH═CH— H 7-F —OCH₂CH₂COOH 522 7-Cl,6-F-Q —CH═CH— H 7-F —SCH₂COOH 523 7-Cl,6-F-Q —CH═CH— H 7-F —SCH₂CH₂COOH 524 7-Cl,6-F-Q —CH═CH— H 7-F —SCH₂CH(CH₃)COOH 525 7-Cl,6-F-Q —CH═CH— H 6-F —OCH₂COOH 526 7-Cl,6-F-Q —CH═CH— H 6-F —OCH(CH₃)COOH 527 7-Cl,6-F-Q —CH═CH— H 6-F —OCH₂CH₂COOH 528 7-Cl,6-F-Q —CH═CH— H 6-F —OCH₂CH(CH3)COOH 529 7-Cl,6-F-Q —CH═CH— H 6-F —OCH₂C(CH₂CH₂)CH₂COOH 530 7-Cl,6-F-Q —CH═CH— H 6-F —SCH₂COOH 531 7-Cl,6-F-Q —CH═CH— H 6-F —SCH(CH₃)COOH 532 7-Cl,6-F-Q —CH═CH— H 6-F —SCH₂CH₂COOH 533 7-Cl,6-F-Q —CH═CH— H 6-F —SCH₂CH(CH₃)COOH 534 7-Cl,6-F-Q —CH═CH— H 6-F —SCH₂C(CH₂CH₂)CH₂COOH 535 7-Cl,6-F-Q —CH═CH— H 9-Cl —OCH₂COOH 536 7-Cl,6-F-Q —CH═CH— H 9-Cl —OCH(CH₃)COOH 537 7-Cl,6-F-Q —CH═CH— H 9-Cl —OCH₂CH₂COOH 538 7-Cl,6-F-Q —CH═CH— H 9-Cl —OCH₂CH(CH3)COOH 539 7-Cl,6-F-Q —CH═CH— H 9-Cl —OCH₂C(CH₂CH₂)CH₂COOH 540 7-Cl,6-F-Q —CH═CH— H 9-Cl —SCH₂COOH 541 7-Cl,6-F-Q —CH═CH— H 9-Cl —SCH(CH₃)COOH 542 7-Cl,6-F-Q —CH═CH— H 9-Cl —SCH₂CH₂COOH 543 7-Cl,6-F-Q —CH═CH— H 9-Cl —SCH₂CH(CH₃)COOH 544 7-Cl,6-F-Q —CH═CH— H 9-Cl —SCH₂C(CH₂CH₂)CH₂COOH 545 7-Cl,6-F-Q —CH═CH— H 8-Cl —SCH₂C(CH₂CH₂)CH₂COOH 546 7-Cl,6-F-Q —CH═CH— H 8-Cl —OCH₂COOH 547 7-Cl,6-F-Q —CH═CH— H 8-Cl —OCH₂CH₂COOH 548 7-Cl,6-F-Q —CH═CH— H 8-Cl —SCH₂COOH 549 7-Cl,6-F-Q —CH═CH— H 8-Cl —SCH₂CH₂COOH 550 7-Cl,6-F-Q —CH═CH— H 8-Cl —SCH₂CH(CH₃)COOH 551 7-Cl,6-F-Q —CH═CH— H 7-Cl —SCH₂C(CH₂CH₂)CH₂COOH 552 7-Cl,6-F-Q —CH═CH— H 7-Cl —OCH₂COOH 553 7-Cl,6-F-Q —CH═CH— H 7-Cl —OCH₂CH₂COOH 554 7-Cl,6-F-Q —CH═CH— H 7-Cl —SCH₂COOH 555 7-Cl,6-F-Q —CH═CH— H 7-Cl —SCH₂CH₂COOH 556 7-Cl,6-F-Q —CH═CH— H 7-Cl —SCH₂CH(CH₃)COOH 557 7-Cl,6-F-Q —CH═CH— H 6-Cl —OCH₂COOH 558 7-Cl,6-F-Q —CH═CH— H 6-Cl —OCH(CH₃)COOH 559 7-Cl,6-F-Q —CH═CH— H 6-Cl —OCH₂CH₂COOH 560 7-Cl,6-F-Q —CH═CH— H 6-Cl —OCH₂CH(CH3)COOH 561 7-Cl,6-F-Q —CH═CH— H 6-Cl —OCH₂C(CH₂CH₂)CH₂COOH 562 7-Cl,6-F-Q —CH═CH— H 6-Cl —SCH₂COOH 563 7-Cl,6-F-Q —CH═CH— H 6-Cl —SCH(CH₃)COOH 564 7-Cl,6-F-Q —CH═CH— H 6-Cl —SCH₂CH₂COOH 565 7-Cl,6-F-Q —CH═CH— H 6-Cl —SCH₂CH(CH₃)COOH 566 7-Cl,6-F-Q —CH═CH— H 6-Cl —SCH₂C(CH₂CH₂)CH₂COOH 567 7-Cl,6-F-Q —CH═CH— H 9-CN —OCH₂COOH 568 7-Cl,6-F-Q —CH═CH— H 9-CN —OCH(CH₃)COOH 569 7-Cl,6-F-Q —CH═CH— H 9-CN —OCH₂CH₂COOH 570 7-Cl,6-F-Q —CH═CH— H 9-CN —OCH₂CH(CH3)COOH 571 7-Cl,6-F-Q —CH═CH— H 9-CN —OCH₂C(CH₂CH₂)CH₂COOH 572 7-Cl,6-F-Q —CH═CH— H 9-CN —SCH₂COOH 573 7-Cl,6-F-Q —CH═CH— H 9-CN —SCH(CH₃)COOH 574 7-Cl,6-F-Q —CH═CH— H 9-CN —SCH₂CH₂COOH 575 7-Cl,6-F-Q —CH═CH— H 9-CN —SCH₂CH(CH₃)COOH 576 7-Cl,6-F-Q —CH═CH— H 9-CN —SCH₂C(CH₂CH₂)CH₂COOH 577 7-Cl,6-F-Q —CH═CH— H 8-CN —OCH₂COOH 578 7-Cl,6-F-Q —CH═CH— H 8-CN —OCH₂CH₂COOH 579 7-Cl,6-F-Q —CH═CH— H 8-CN —SCH₂COOH 580 7-Cl,6-F-Q —CH═CH— H 8-CN —SCH₂CH₂COOH 581 7-Cl,6-F-Q —CH═CH— H 8-CN —SCH₂CH(CH₃)COOH 582 7-Cl,6-F-Q —CH═CH— H 8-CN —SCH₂C(CH₂CH₂)CH₂COOH 583 7-Cl,6-F-Q —CH═CH— H 7-CN —OCH₂COOH 584 7-Cl,6-F-Q —CH═CH— H 7-CN —OCH₂CH₂COOH 585 7-Cl,6-F-Q —CH═CH— H 7-CN —SCH₂COOH 586 7-Cl,6-F-Q —CH═CH— H 7-CN —SCH₂CH₂COOH 587 7-Cl,6-F-Q —CH═CH— H 7-CN —SCH₂CH(CH₃)COOH 588 7-Cl,6-F-Q —CH═CH— H 9-CH₃ —OCH₂COOH 589 7-Cl,6-F-Q —CH═CH— H 9-CH₃ —OCH₂CH₂COOH 590 7-Cl,6-F-Q —CH═CH— H 9-CH₃ —SCH₂COOH 591 7-Cl,6-F-Q —CH═CH— H 9-CH₃ —SCH₂CH₂COOH 592 7-Cl,6-F-Q —CH═CH— H 9-CH₃ —SCH₂CH(CH₃)COOH 593 7-Cl,6-F-Q —CH═CH— H 9-CH₃ —SCH₂CH(CH₂CH₃)COOH 594 7-Cl,6-F-Q —CH═CH— H 9-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 595 7-Cl,6-F-Q —CH═CH— H 8-CH₃ —OCH₂COOH 596 7-Cl,6-F-Q —CH═CH— H 8-CH₃ —OCH₂CH₂COOH 597 7-Cl,6-F-Q —CH═CH— H 8-CH₃ —SCH₂COOH 598 7-Cl,6-F-Q —CH═CH— H 8-CH₃ —SCH₂CH₂COOH 599 7-Cl,6-F-Q —CH═CH— H 8-CH₃ —SCH₂CH(CH₃)COOH 600 7-Cl,6-F-Q —CH═CH— H 8-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 601 7-Cl,6-F-Q —CH═CH— H 7-CH₃ —OCH₂COOH 602 7-Cl,6-F-Q —CH═CH— H 7-CH₃ —OCH₂CH₂COOH 603 7-Cl,6-F-Q —CH═CH— H 7-CH₃ —SCH₂COOH 604 7-Cl,6-F-Q —CH═CH— H 7-CH₃ —SCH₂CH₂COOH 605 7-Cl,6-F-Q —CH═CH— H 7-CH₃ —SCH₂CH(CH₃)COOH 606 7-Cl,6-F-Q —CH═CH— H 9-CF₃ —OCH₂COOH 607 7-Cl,6-F-Q —CH═CH— H 9-CF₃ —OCH(CH₃)COOH 608 7-Cl,6-F-Q —CH═CH— H 9-CF₃ —OCH₂CH₂COOH 609 7-Cl,6-F-Q —CH═CH— H 9-CF₃ —OCH₂CH(CH3)COOH 610 7-Cl,6-F-Q —CH═CH— H 9-CF₃ —OCH₂C(CH₂CH₂)CH₂COOH 611 7-Cl,6-F-Q —CH═CH— H 9-CF₃ —SCH₂COOH 612 7-Cl,6-F-Q —CH═CH— H 9-CF₃ —SCH(CH₃)COOH 613 7-Cl,6-F-Q —CH═CH— H 9-CF₃ —SCH₂CH₂COOH 614 7-Cl,6-F-Q —CH═CH— H 9-CF₃ —SCH₂CH(CH₃)COOH 615 7-Cl,6-F-Q —CH═CH— H 9-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 616 7-Cl,6-F-Q —CH═CH— H 8-CF₃ —OCH₂COOH 617 7-Cl,6-F-Q —CH═CH— H 8-CF₃ —OCH₂CH₂COOH 618 7-Cl,6-F-Q —CH═CH— H 8-CF₃ —SCH₂COOH 619 7-Cl,6-F-Q —CH═CH— H 8-CF₃ —SCH₂CH₂COOH 620 7-Cl,6-F-Q —CH═CH— H 8-CF₃ —SCH₂CH(CH₃)COOH 621 7-Cl,6-F-Q —CH═CH— H 8-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 622 7-Cl,6-F-Q —CH═CH— H 7-CF₃ —OCH₂COOH 623 7-Cl,6-F-Q —CH═CH— H 7-CF₃ —OCH₂CH₂COOH 624 7-Cl,6-F-Q —CH═CH— H 7-CF₃ —SCH₂COOH 625 7-Cl,6-F-Q —CH═CH— H 7-CF₃ —SCH₂CH₂COOH 626 7-Cl,6-F-Q —CH═CH— H 7-CF₃ —SCH₂CH(CH₃)COOH 627 7-Cl,6-F-Q —CH═CH— H 9-C≡CH —OCH₂COOH 628 7-Cl,6-F-Q —CH═CH— H 9-C≡CH —OCH(CH₃)COOH 629 7-Cl,6-F-Q —CH═CH— H 9-C≡CH —OCH₂CH₂COOH 630 7-Cl,6-F-Q —CH═CH— H 9-C≡CH —OCH₂CH(CH3)COOH 631 7-Cl,6-F-Q —CH═CH— H 9-C≡CH —OCH₂C(CH₂CH₂)CH₂COOH 632 7-Cl,6-F-Q —CH═CH— H 9-C≡CH —SCH₂COOH 633 7-Cl,6-F-Q —CH═CH— H 9-C≡CH —SCH(CH₃)COOH 634 7-Cl,6-F-Q —CH═CH— H 9-C≡CH —SCH₂CH₂COOH 635 7-Cl,6-F-Q —CH═CH— H 9-C≡CH —SCH₂CH(CH₃)COOH 636 7-Cl,6-F-Q —CH═CH— H 9-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 637 7-Cl,6-F-Q —CH═CH— H 8-C≡CH —OCH₂COOH 638 7-Cl,6-F-Q —CH═CH— H 8-C≡CH —OCH₂CH₂COOH 639 7-Cl,6-F-Q —CH═CH— H 8-C≡CH —SCH₂COOH 640 7-Cl,6-F-Q —CH═CH— H 8-C≡CH —SCH₂CH₂COOH 641 7-Cl,6-F-Q —CH═CH— H 8-C≡CH —SCH₂CH(CH₃)COOH 642 7-Cl,6-F-Q —CH═CH— H 8-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 643 7-Cl,6-F-Q —CH═CH— H 7-C≡CH —OCH₂COOH 644 7-Cl,6-F-Q —CH═CH— H 7-C≡CH —OCH₂CH₂COOH 645 7-Cl,6-F-Q —CH═CH— H 7-C≡CH —SCH₂COOH 646 7-Cl,6-F-Q —CH═CH— H 7-C≡CH —SCH₂CH₂COOH 647 7-Cl,6-F-Q —CH═CH— H 7-C≡CH —SCH₂CH(CH₃)COOH 648 7-Cl,6-F-Q —CH═CH— H 9-CH₂OH —OCH₂COOH 649 7-Cl,6-F-Q —CH═CH— H 9-CH₂OH —SCH₂CH₂COOH 650 7-Cl,6-F-Q —CH═CH— H 8-CH₂OH —OCH₂COOH 651 7-Cl,6-F-Q —CH═CH— H 8-CH₂OH —SCH₂CH₂COOH 652 7-Cl,6-F-Q —CH═CH— H 7-CH₂OH —OCH₂COOH 653 7-Cl,6-F-Q —CH═CH— H 7-CH₂OH —SCH₂CH₂COOH 654 7-Cl,6-F-Q —CH═CH— H 9- —OCH₂COOH C(CH₃)₂OH 655 7-Cl,6-F-Q —CH═CH— H 9- —SCH₂CH₂COOH C(CH₃)₂OH 656 7-Cl,6-F-Q —CH═CH— H 8- —OCH₂COOH C(CH₃)₂OH 657 7-Cl,6-F-Q —CH═CH— H 8- —SCH₂CH₂COOH C(CH₃)₂OH 658 7-Cl,6-F-Q —CH═CH— H 7- —OCH₂COOH C(CH₃)₂OH 659 7-Cl,6-F-Q —CH═CH— H 7- —SCH₂CH₂COOH C(CH₃)₂OH 660 7-Cl,6-F-Q —CH═CH— H 9-OCH₃ —OCH₂COOH 661 7-Cl,6-F-Q —CH═CH— H 9-OCH₃ —SCH₂CH₂COOH 662 7-Cl,6-F-Q —CH═CH— H 8-OCH₃ —OCH₂COOH 663 7-Cl,6-F-Q —CH═CH— H 8-OCH₃ —SCH₂CH₂COOH 664 7-Cl,6-F-Q —CH═CH— H 7-OCH₃ —OCH₂COOH 665 7-Cl,6-F-Q —CH═CH— H 7-OCH₃ —SCH₂CH₂COOH 666 7-Cl,6-F-Q —CH═CH— H 9-OCHF₂ —OCH₂COOH 667 7-Cl,6-F-Q —CH═CH— H 9-OCHF₂ —SCH₂CH₂COOH 668 7-Cl,6-F-Q —CH═CH— H 8-OCHF₂ —OCH₂COOH 669 7-Cl,6-F-Q —CH═CH— H 8-OCHF₂ —SCH₂CH₂COOH 670 7-Cl,6-F-Q —CH═CH— H 7-OCHF₂ —OCH₂COOH 671 7-Cl,6-F-Q —CH═CH— H 7-OCHF₂ —SCH₂CH₂COOH 672 7-Cl,6-F-Q —CH═CH— H 9-OCF₃ —OCH₂COOH 673 7-Cl,6-F-Q —CH═CH— H 9-OCF₃ —SCH₂CH₂COOH 674 7-Cl,6-F-Q —CH═CH— H 8-OCF₃ —OCH₂COOH 675 7-Cl,6-F-Q —CH═CH— H 8-OCF₃ —SCH₂CH₂COOH 676 7-Cl,6-F-Q —CH═CH— H 7-OCF₃ —OCH₂COOH 677 7-Cl,6-F-Q —CH═CH— H 7-OCF₃ —SCH₂CH₂COOH 678 7-Cl,6-F-Q —CH═CH— H 9-SOCH₃ —OCH₂COOH 679 7-Cl,6-F-Q —CH═CH— H 9-SOCH₃ —SCH₂CH₂COOH 680 7-Cl,6-F-Q —CH═CH— H 8-SOCH₃ —OCH₂COOH 681 7-Cl,6-F-Q —CH═CH— H 8-SOCH₃ —SCH₂CH₂COOH 682 7-Cl,6-F-Q —CH═CH— H 7-SOCH₃ —OCH₂COOH 683 7-Cl,6-F-Q —CH═CH— H 7-SOCH₃ —SCH₂CH₂COOH 684 7-Cl,6-F-Q —CH═CH— H 9-SO₂CH₃ —OCH₂COOH 685 7-Cl,6-F-Q —CH═CH— H 9-SO₂CH₃ —SCH₂CH₂COOH 686 7-Cl,6-F-Q —CH═CH— H 8-SO₂CH₃ —OCH₂COOH 687 7-Cl,6-F-Q —CH═CH— H 8-SO₂CH₃ —SCH₂CH₂COOH 688 7-Cl,6-F-Q —CH═CH— H 7-SO₂CH₃ —OCH₂COOH 689 7-Cl,6-F-Q —CH═CH— H 7-SO₂CH₃ —SCH₂CH₂COOH 690 7-Cl,6-F-Q —CH═CH— H 9-CH═CH₂ —SCH₂CH₂COOH 691 7-Cl,6-F-Q —CH═CH— H 8-CH═CH₂ —SCH₂CH₂COOH 692 7-Cl,6-F-Q —CH═CH— H 7-CH═CH₂ —SCH₂CH₂COOH 693 7-Cl,6-F-Q —CH═CH— H 9-NO₂ —OCH₂COOH 694 7-Cl,6-F-Q —CH═CH— H 9-NO₂ —SCH₂CH₂COOH 695 7-Cl,6-F-Q —CH═CH— H 8-NO₂ —OCH₂COOH 696 7-Cl,6-F-Q —CH═CH— H 8-NO₂ —SCH₂CH₂COOH 697 7-Cl,6-F-Q —CH═CH— H 7-NO₂ —OCH₂COOH 698 7-Cl,6-F-Q —CH═CH— H 7-NO₂ —SCH₂CH₂COOH 699 7-Cl,6-F-Q —CH═CH— 1-F H —SCH₂CH₂COOH 700 7-Cl,6-F-Q —CH═CH— 2-F H —SCH₂CH₂COOH 701 7-Cl,6-F-Q —CH═CH— 1-Cl H —SCH₂CH₂COOH 702 7-Cl,6-F-Q —CH═CH— 2-Cl H —SCH₂CH₂COOH 703 7-Cl,6-F-Q —CH═CH— 1-CH₃ H —SCH₂CH₂COOH 704 7-Cl,6-F-Q —CH═CH— 2-CH₃ H —SCH₂CH₂COOH 705 7-Cl,6-F-Q —CH═CH— 1-OCH₃ H —SCH₂CH₂COOH 706 7-Cl,6-F-Q —CH═CH— 2-OCH₃ H —SCH₂CH₂COOH 707 7-Cl,6-F-Q —CH═CH— 1-NO₂ H —SCH₂CH₂COOH 708 7-Cl,6-F-Q —CH═CH— 2-NO₂ H —SCH₂CH₂COOH 709 7-Cl,6-F-Q —CH═CH— 1-CN H —SCH₂CH₂COOH 710 7-Cl,6-F-Q —CH═CH— 2-CN H —SCH₂CH₂COOH 711 7-Cl,6-F-Q —CH₂O— H H —OCH₂COOH 712 7-Cl,6-F-Q —CH₂O— H H —OCH(CH3)COOH 713 7-Cl,6-F-Q —CH₂O— H H —OCH₂CH₂COOH 714 7-Cl,6-F-Q —CH₂O— H H —OCH₂CH(CH₃)COOH 715 7-Cl,6-F-Q —CH₂O— H H —OCH₂C(CH₂CH₂)CH₂COOH 716 7-Cl,6-F-Q —CH₂O— H H —SCH₂COOH 717 7-Cl,6-F-Q —CH₂O— H H —SCH(CH3)COOH 718 7-Cl,6-F-Q —CH₂O— H H —SCH₂CH₂COOH 719 7-Cl,6-F-Q —CH₂O— H H —SCH₂CH(CH₃)COOH 720 7-Cl,6-F-Q —CH₂O— H H —SCH₂C(CH₃)₂COOH 721 7-Cl,6-F-Q —CH₂O— H H —SCH₂CH(CH₂CH₃)COOH 722 7-Cl,6-F-Q —CH₂O— H H —SCH(CH₃)CH₂COOH 723 7-Cl,6-F-Q —CH₂O— H H —SC(CH₃)₂CH₂COOH 724 7-Cl,6-F-Q —CH₂O— H H —SCH₂CH₂CH₂COOH 725 7-Cl,6-F-Q —CH₂O— H H —SCH₂CH(CH₃)CH₂COOH 726 7-Cl,6-F-Q —CH₂O— H H —SCH₂C(CH₃)₂CH₂COOH 727 7-Cl,6-F-Q —CH₂O— H H —SCH₂C(CH₂CH₂)CH₂COOH 728 7-Cl,6-F-Q —CH₂O— H H —SCH₂CF₂COOH 729 7-Cl,6-F-Q —CH₂O— H H —SCH₂CF₂CH₂COOH 730 7-Cl,6-F-Q —CH₂O— H H —SCH₂-Tet 731 7-Cl,6-F-Q —CH₂O— H H —SCH₂CH₂-Tet 732 7-Cl,6-F-Q —CH₂O— H H —SCH₂NHSO₂CF₃ 733 7-Cl,6-F-Q —CH₂O— H H —SCH₂CONHSO₂CH₃ 734 7-Cl,6-F-Q —CH₂O— H H —SCH₂CONHSO₂CF₃ 735 7-Cl,6-F-Q —CH₂O— H H —SCH₂CONHSO₂Ph 736 7-Cl,6-F-Q —CH₂O— H H —SCH₂CONHSO₂(2-CH₃—Ph) 737 7-Cl,6-F-Q —CH₂O— H H —SCH₂CH₂NHSO₂CF₃ 738 7-Cl,6-F-Q —CH₂O— H H —SCH₂CH₂CONHSO₂CH₃ 739 7-Cl,6-F-Q —CH₂O— H H —SCH₂CH₂CONHSO₂CF₃ 740 7-Cl,6-F-Q —CH₂O— H H —SCH₂CH₂CONHSO₂Ph 741 7-Cl,6-F-Q —CH₂O— H H —SCH₂CH₂CONHSO₂(2-CH₃—Ph) 742 7-Cl,6-F-Q —CH₂O— H H —CH₂COOH 743 7-Cl,6-F-Q —CH₂O— H H —CH₂CH₂COOH 744 7-Cl,6-F-Q —CH₂O— H H —CH₂CH₂CH₂COOH 745 7-Cl,6-F-Q —CH₂O— H 9-F —OCH₂COOH 746 7-Cl,6-F-Q —CH₂O— H 9-F —OCH(CH₃)COOH 747 7-Cl,6-F-Q —CH₂O— H 9-F —OCH₂CH₂COOH 748 7-Cl,6-F-Q —CH₂O— H 9-F —OCH₂CH(CH3)COOH 749 7-Cl,6-F-Q —CH₂O— H 9-F —OCH₂C(CH₂CH₂)CH₂COOH 750 7-Cl,6-F-Q —CH₂O— H 9-F —SCH₂COOH 751 7-Cl,6-F-Q —CH₂O— H 9-F —SCH(CH₃)COOH 752 7-Cl,6-F-Q —CH₂O— H 9-F —SCH₂CH₂COOH 753 7-Cl,6-F-Q —CH₂O— H 9-F —SCH₂CH(CH₃)COOH 754 7-Cl,6-F-Q —CH₂O— H 9-F —SCH₂C(CH₂CH₂)CH₂COOH 755 7-Cl,6-F-Q —CH₂O— H 8-F —OCH₂COOH 756 7-Cl,6-F-Q —CH₂O— H 8-F —OCH₂CH₂COOH 757 7-Cl,6-F-Q —CH₂O— H 8-F —SCH₂COOH 758 7-Cl,6-F-Q —CH₂O— H 8-F —SCH₂CH₂COOH 759 7-Cl,6-F-Q —CH₂O— H 8-F —SCH₂CH(CH₃)COOH 760 7-Cl,6-F-Q —CH₂O— H 8-F —SCH₂C(CH₂CH₂)CH₂COOH 761 7-Cl,6-F-Q —CH₂O— H 7-F —OCH₂COOH 762 7-Cl,6-F-Q —CH₂O— H 7-F —OCH₂CH₂COOH 763 7-Cl,6-F-Q —CH₂O— H 7-F —SCH₂COOH 764 7-Cl,6-F-Q —CH₂O— H 7-F —SCH₂CH₂COOH 765 7-Cl,6-F-Q —CH₂O— H 7-F —SCH₂CH(CH₃)COOH 766 7-Cl,6-F-Q —CH₂O— H 6-F —OCH₂COOH 767 7-Cl,6-F-Q —CH₂O— H 6-F —OCH(CH₃)COOH 768 7-Cl,6-F-Q —CH₂O— H 6-F —OCH₂CH₂COOH 769 7-Cl,6-F-Q —CH₂O— H 6-F —OCH₂CH(CH3)COOH 770 7-Cl,6-F-Q —CH₂O— H 6-F —OCH₂C(CH₂CH₂)CH₂COOH 771 7-Cl,6-F-Q —CH₂O— H 6-F —SCH₂COOH 772 7-Cl,6-F-Q —CH₂O— H 6-F —SCH(CH₃)COOH 773 7-Cl,6-F-Q —CH₂O— H 6-F —SCH₂CH₂COOH 774 7-Cl,6-F-Q —CH₂O— H 6-F —SCH₂CH(CH₃)COOH 775 7-Cl,6-F-Q —CH₂O— H 6-F —SCH₂C(CH₂CH₂)CH₂COOH 776 7-Cl,6-F-Q —CH₂O— H 9-Cl —OCH₂COOH 777 7-Cl,6-F-Q —CH₂O— H 9-Cl —OCH(CH₃)COOH 778 7-Cl,6-F-Q —CH₂O— H 9-Cl —OCH₂CH₂COOH 779 7-Cl,6-F-Q —CH₂O— H 9-Cl —OCH₂CH(CH3)COOH 780 7-Cl,6-F-Q —CH₂O— H 9-Cl —OCH₂C(CH₂CH₂)CH₂COOH 781 7-Cl,6-F-Q —CH₂O— H 9-Cl —SCH₂COOH 782 7-Cl,6-F-Q —CH₂O— H 9-Cl —SCH(CH₃)COOH 783 7-Cl,6-F-Q —CH₂O— H 9-Cl —SCH₂CH₂COOH 784 7-Cl,6-F-Q —CH₂O— H 9-Cl —SCH₂CH(CH₃)COOH 785 7-Cl,6-F-Q —CH₂O— H 9-Cl —SCH₂C(CH₂CH₂)CH₂COOH 786 7-Cl,6-F-Q —CH₂O— H 8-Cl —SCH₂C(CH₂CH₂)CH₂COOH 787 7-Cl,6-F-Q —CH₂O— H 8-Cl —OCH₂COOH 788 7-Cl,6-F-Q —CH₂O— H 8-Cl —OCH₂CH₂COOH 789 7-Cl,6-F-Q —CH₂O— H 8-Cl —SCH₂COOH 790 7-Cl,6-F-Q —CH₂O— H 8-Cl —SCH₂CH₂COOH 791 7-Cl,6-F-Q —CH₂O— H 8-Cl —SCH₂CH(CH₃)COOH 792 7-Cl,6-F-Q —CH₂O— H 7-Cl —OCH₂COOH 793 7-Cl,6-F-Q —CH₂O— H 7-Cl —OCH₂CH₂COOH 794 7-Cl,6-F-Q —CH₂O— H 7-Cl —SCH₂COOH 795 7-Cl,6-F-Q —CH₂O— H 7-Cl —SCH₂CH₂COOH 796 7-Cl,6-F-Q —CH₂O— H 7-Cl —SCH₂CH(CH₃)COOH 797 7-Cl,6-F-Q —CH₂O— H 9-CN —OCH₂COOH 798 7-Cl,6-F-Q —CH₂O— H 9-CN —OCH(CH₃)COOH 799 7-Cl,6-F-Q —CH₂O— H 9-CN —OCH₂CH₂COOH 800 7-Cl,6-F-Q —CH₂O— H 9-CN —OCH₂CH(CH3)COOH 801 7-Cl,6-F-Q —CH₂O— H 9-CN —OCH₂C(CH₂CH₂)CH₂COOH 802 7-Cl,6-F-Q —CH₂O— H 9-CN —SCH₂COOH 803 7-Cl,6-F-Q —CH₂O— H 9-CN —SCH(CH₃)COOH 804 7-Cl,6-F-Q —CH₂O— H 9-CN —SCH₂CH₂COOH 805 7-Cl,6-F-Q —CH₂O— H 9-CN —SCH₂CH(CH₃)COOH 806 7-Cl,6-F-Q —CH₂O— H 9-CN —SCH₂C(CH₂CH₂)CH₂COOH 807 7-Cl,6-F-Q —CH₂O— H 8-CN —OCH₂COOH 808 7-Cl,6-F-Q —CH₂O— H 8-CN —OCH₂CH₂COOH 809 7-Cl,6-F-Q —CH₂O— H 8-CN —SCH₂COOH 810 7-Cl,6-F-Q —CH₂O— H 8-CN —SCH₂CH₂COOH 811 7-Cl,6-F-Q —CH₂O— H 8-CN —SCH₂CH(CH₃)COOH 812 7-Cl,6-F-Q —CH₂O— H 8-CN —SCH₂C(CH₂CH₂)CH₂COOH 813 7-Cl,6-F-Q —CH₂O— H 7-CN —OCH₂COOH 814 7-Cl,6-F-Q —CH₂O— H 7-CN —OCH₂CH₂COOH 815 7-Cl,6-F-Q —CH₂O— H 7-CN —SCH₂COOH 816 7-Cl,6-F-Q —CH₂O— H 7-CN —SCH₂CH₂COOH 817 7-Cl,6-F-Q —CH₂O— H 7-CN —SCH₂CH(CH₃)COOH 818 7-Cl,6-F-Q —CH₂O— H 9-CH₃ —OCH₂COOH 819 7-Cl,6-F-Q —CH₂O— H 9-CH₃ —OCH₂CH₂COOH 820 7-Cl,6-F-Q —CH₂O— H 9-CH₃ —SCH₂COOH 821 7-Cl,6-F-Q —CH₂O— H 9-CH₃ —SCH₂CH₂COOH 822 7-Cl,6-F-Q —CH₂O— H 9-CH₃ —SCH₂CH(CH₃)COOH 823 7-Cl,6-F-Q —CH₂O— H 9-CH₃ —SCH₂CH(CH₂CH₃)COOH 824 7-Cl,6-F-Q —CH₂O— H 9-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 825 7-Cl,6-F-Q —CH₂O— H 8-CH₃ —OCH₂COOH 826 7-Cl,6-F-Q —CH₂O— H 8-CH₃ —OCH₂CH₂COOH 827 7-Cl,6-F-Q —CH₂O— H 8-CH₃ —SCH₂COOH 828 7-Cl,6-F-Q —CH₂O— H 8-CH₃ —SCH₂CH₂COOH 829 7-Cl,6-F-Q —CH₂O— H 8-CH₃ —SCH₂CH(CH₃)COOH 830 7-Cl,6-F-Q —CH₂O— H 8-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 831 7-Cl,6-F-Q —CH₂O— H 7-CH₃ —OCH₂COOH 832 7-Cl,6-F-Q —CH₂O— H 7-CH₃ —OCH₂CH₂COOH 833 7-Cl,6-F-Q —CH₂O— H 7-CH₃ —SCH₂COOH 834 7-Cl,6-F-Q —CH₂O— H 7-CH₃ —SCH₂CH₂COOH 835 7-Cl,6-F-Q —CH₂O— H 7-CH₃ —SCH₂CH(CH₃)COOH 836 7-Cl,6-F-Q —CH₂O— H 9-CF₃ —OCH₂COOH 837 7-Cl,6-F-Q —CH₂O— H 9-CF₃ —OCH(CH₃)COOH 838 7-Cl,6-F-Q —CH₂O— H 9-CF₃ —OCH₂CH₂COOH 839 7-Cl,6-F-Q —CH₂O— H 9-CF₃ —OCH₂CH(CH3)COOH 840 7-Cl,6-F-Q —CH₂O— H 9-CF₃ —OCH₂C(CH₂CH₂)CH₂COOH 841 7-Cl,6-F-Q —CH₂O— H 9-CF₃ —SCH₂COOH 842 7-Cl,6-F-Q —CH₂O— H 9-CF₃ —SCH(CH₃)COOH 843 7-Cl,6-F-Q —CH₂O— H 9-CF₃ —SCH₂CH₂COOH 844 7-Cl,6-F-Q —CH₂O— H 9-CF₃ —SCH₂CH(CH₃)COOH 845 7-Cl,6-F-Q —CH₂O— H 9-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 846 7-Cl,6-F-Q —CH₂O— H 8-CF₃ —OCH₂COOH 847 7-Cl,6-F-Q —CH₂O— H 8-CF₃ —OCH₂CH₂COOH 848 7-Cl,6-F-Q —CH₂O— H 8-CF₃ —SCH₂COOH 849 7-Cl,6-F-Q —CH₂O— H 8-CF₃ —SCH₂CH₂COOH 850 7-Cl,6-F-Q —CH₂O— H 8-CF₃ —SCH₂CH(CH₃)COOH 851 7-Cl,6-F-Q —CH₂O— H 8-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 852 7-Cl,6-F-Q —CH₂O— H 7-CF₃ —OCH₂COOH 853 7-Cl,6-F-Q —CH₂O— H 7-CF₃ —OCH₂CH₂COOH 854 7-Cl,6-F-Q —CH₂O— H 7-CF₃ —SCH₂COOH 855 7-Cl,6-F-Q —CH₂O— H 7-CF₃ —SCH₂CH₂COOH 856 7-Cl,6-F-Q —CH₂O— H 7-CF₃ —SCH₂CH(CH₃)COOH 857 7-Cl,6-F-Q —CH₂O— H 9-C≡CH —OCH₂COOH 858 7-Cl,6-F-Q —CH₂O— H 9-C≡CH —OCH(CH₃)COOH 859 7-Cl,6-F-Q —CH₂O— H 9-C≡CH —OCH₂CH₂COOH 860 7-Cl,6-F-Q —CH₂O— H 9-C≡CH —OCH₂CH(CH3)COOH 861 7-Cl,6-F-Q —CH₂O— H 9-C≡CH —OCH₂C(CH₂CH₂)CH₂COOH 862 7-Cl,6-F-Q —CH₂O— H 9-C≡CH —SCH₂COOH 863 7-Cl,6-F-Q —CH₂O— H 9-C≡CH —SCH(CH₃)COOH 864 7-Cl,6-F-Q —CH₂O— H 9-C≡CH —SCH₂CH₂COOH 865 7-Cl,6-F-Q —CH₂O— H 9-C≡CH —SCH₂CH(CH₃)COOH 866 7-Cl,6-F-Q —CH₂O— H 9-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 867 7-Cl,6-F-Q —CH₂O— H 8-C≡CH —OCH₂COOH 868 7-Cl,6-F-Q —CH₂O— H 8-C≡CH —OCH₂CH₂COOH 869 7-Cl,6-F-Q —CH₂O— H 8-C≡CH —SCH₂COOH 870 7-Cl,6-F-Q —CH₂O— H 8-C≡CH —SCH₂CH₂COOH 871 7-Cl,6-F-Q —CH₂O— H 8-C≡CH —SCH₂CH(CH₃)COOH 872 7-Cl,6-F-Q —CH₂O— H 8-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 873 7-Cl,6-F-Q —CH₂O— H 7-C≡CH —OCH₂COOH 874 7-Cl,6-F-Q —CH₂O— H 7-C≡CH —OCH₂CH₂COOH 875 7-Cl,6-F-Q —CH₂O— H 7-C≡CH —SCH₂COOH 876 7-Cl,6-F-Q —CH₂O— H 7-C≡CH —SCH₂CH₂COOH 877 7-Cl,6-F-Q —CH₂O— H 7-C≡CH —SCH₂CH(CH₃)COOH 878 7-Cl,6-F-Q —CH₂O— H 9-CH₂OH —OCH₂COOH 879 7-Cl,6-F-Q —CH₂O— H 9-CH₂OH —SCH₂CH₂COOH 880 7-Cl,6-F-Q —CH₂O— H 8-CH₂OH —OCH₂COOH 881 7-Cl,6-F-Q —CH₂O— H 8-CH₂OH —SCH₂CH₂COOH 885 7-Cl,6-F-Q —CH₂O— H 9- —SCH₂CH₂COOH C(CH₃)₂OH 886 7-Cl,6-F-Q —CH₂O— H 8- —OCH₂COOH C(CH₃)₂OH 887 7-Cl,6-F-Q —CH₂O— H 8- —SCH₂CH₂COOH C(CH₃)₂OH 888 7-Cl,6-F-Q —CH₂O— H 7- —OCH₂COOH C(CH₃)₂OH 889 7-Cl,6-F-Q —CH₂O— H 7- —SCH₂CH₂COOH C(CH₃)₂OH 890 7-Cl,6-F-Q —CH₂O— H 9-OCH₃ —OCH₂COOH 891 7-Cl,6-F-Q —CH₂O— H 9-OCH₃ —SCH₂CH₂COOH 892 7-Cl,6-F-Q —CH₂O— H 8-OCH₃ —OCH₂COOH 893 7-Cl,6-F-Q —CH₂O— H 8-OCH₃ —SCH₂CH₂COOH 894 7-Cl,6-F-Q —CH₂O— H 7-OCH₃ —OCH₂COOH 895 7-Cl,6-F-Q —CH₂O— H 7-OCH₃ —SCH₂CH₂COOH 896 7-Cl,6-F-Q —CH₂O— H 9-OCHF₂ —OCH₂COOH 897 7-Cl,6-F-Q —CH₂O— H 9-OCHF₂ —SCH₂CH₂COOH 898 7-Cl,6-F-Q —CH₂O— H 8-OCHF₂ —OCH₂COOH 899 7-Cl,6-F-Q —CH₂O— H 8-OCHF₂ —SCH₂CH₂COOH 900 7-Cl,6-F-Q —CH₂O— H 7-OCHF₂ —OCH₂COOH 901 7-Cl,6-F-Q —CH₂O— H 7-OCHF₂ —SCH₂CH₂COOH 902 7-Cl,6-F-Q —CH₂O— H 9-OCF₃ —OCH₂COOH 903 7-Cl,6-F-Q —CH₂O— H 9-OCF₃ —SCH₂CH₂COOH 904 7-Cl,6-F-Q —CH₂O— H 8-OCF₃ —OCH₂COOH 905 7-Cl,6-F-Q —CH₂O— H 8-OCF₃ —SCH₂CH₂COOH 906 7-Cl,6-F-Q —CH₂O— H 7-OCF₃ —OCH₂COOH 907 7-Cl,6-F-Q —CH₂O— H 7-OCF₃ —SCH₂CH₂COOH 908 7-Cl,6-F-Q —CH₂O— H 9-SOCH₃ —OCH₂COOH 909 7-Cl,6-F-Q —CH₂O— H 9-SOCH₃ —SCH₂CH₂COOH 910 7-Cl,6-F-Q —CH₂O— H 8-SOCH₃ —OCH₂COOH 911 7-Cl,6-F-Q —CH₂O— H 8-SOCH₃ —SCH₂CH₂COOH 912 7-Cl,6-F-Q —CH₂O— H 7-SOCH₃ —OCH₂COOH 913 7-Cl,6-F-Q —CH₂O— H 7-SOCH₃ —SCH₂CH₂COOH 914 7-Cl,6-F-Q —CH₂O— H 9-SO₂CH₃ —OCH₂COOH 915 7-Cl,6-F-Q —CH₂O— H 9-SO₂CH₃ —SCH₂CH₂COOH 916 7-Cl,6-F-Q —CH₂O— H 8-SO₂CH₃ —OCH₂COOH 917 7-Cl,6-F-Q —CH₂O— H 8-SO₂CH₃ —SCH₂CH₂COOH 918 7-Cl,6-F-Q —CH₂O— H 7-SO₂CH₃ —OCH₂COOH 919 7-Cl,6-F-Q —CH₂O— H 7-SO₂CH₃ —SCH₂CH₂COOH 920 7-Cl,6-F-Q —CH₂O— H 9-CH═CH₂ —SCH₂CH₂COOH 921 7-Cl,6-F-Q —CH₂O— H 8-CH═CH₂ —SCH₂CH₂COOH 922 7-Cl,6-F-Q —CH₂O— H 7-CH═CH₂ —SCH₂CH₂COOH 923 7-Cl,6-F-Q —CH₂O— H 9-NO₂ —OCH₂COOH 924 7-Cl,6-F-Q —CH₂O— H 9-NO₂ —SCH₂CH₂COOH 925 7-Cl,6-F-Q —CH₂O— H 8-NO₂ —OCH₂COOH 926 7-Cl,6-F-Q —CH₂O— H 8-NO₂ —SCH₂CH₂COOH 927 7-Cl,6-F-Q —CH₂O— H 7-NO₂ —OCH₂COOH 928 7-Cl,6-F-Q —CH₂O— H 7-NO₂ —SCH₂CH₂COOH 929 7-Cl,6-F-Q —CH₂O— 1-F H —SCH₂CH₂COOH 930 7-Cl,6-F-Q —CH₂O— 2-F H —SCH₂CH₂COOH 931 7-Cl,6-F-Q —CH₂O— 1-Cl H —SCH₂CH₂COOH 932 7-Cl,6-F-Q —CH₂O— 2-Cl H —SCH₂CH₂COOH 933 7-Cl,6-F-Q —CH₂O— 1-CH₃ H —SCH₂CH₂COOH 934 7-Cl,6-F-Q —CH₂O— 2-CH₃ H —SCH₂CH₂COOH 935 7-Cl,6-F-Q —CH₂O— 1-OCH₃ H —SCH₂CH₂COOH 936 7-Cl,6-F-Q —CH₂O— 2-OCH₃ H —SCH₂CH₂COOH 937 7-Cl,6-F-Q —CH₂O— 1-NO₂ H —SCH₂CH₂COOH 938 7-Cl,6-F-Q —CH₂O— 2-NO₂ H —SCH₂CH₂COOH 939 7-Cl,6-F-Q —CH₂O— 1-CN H —SCH₂CH₂COOH 940 7-Cl,6-F-Q —CH₂O— 2-CN H —SCH₂CH₂COOH 941 7-F-Q —CH═CH— H H —OCH₂COOH 942 7-F-Q —CH═CH— H H —OCH(CH₃)COOH 943 7-F-Q —CH═CH— H H —OCH₂CH₂COOH 944 7-F-Q —CH═CH— H H —OCH₂CH(CH₃)COOH 945 7-F-Q —CH═CH— H H —OCH₂C(CH₂CH₂)CH₂COOH 946 7-F-Q —CH═CH— H H —SCH₂COOH 947 7-F-Q —CH═CH— H H —SCH(CH₃)COOH 948 7-F-Q —CH═CH— H H —SCH₂CH₂COOH 949 7-F-Q —CH═CH— H H —SCH₂CH(CH₃)COOH 950 7-F-Q —CH═CH— H H —SCH₂C(CH₃)₂COOH 951 7-F-Q —CH═CH— H H —SCH₂CH(CH₂CH₃)COOH 952 7-F-Q —CH═CH— H H —SCH(CH₃)CH₂COOH 953 7-F-Q —CH═CH— H H —SC(CH₃)₂CH₂COOH 954 7-F-Q —CH═CH— H H —SCH₂CH₂CH₂COOH 955 7-F-Q —CH═CH— H H —SCH₂CH(CH₃)CH₂COOH 956 7-F-Q —CH═CH— H H —SCH₂C(CH₃)₂CH₂COOH 957 7-F-Q —CH═CH— H H —SCH₂C(CH₂CH₂)CH₂COOH 958 7-F-Q —CH═CH— H H —SCH₂CF₂COOH 959 7-F-Q —CH═CH— H H —SCH₂CF₂CH₂COOH 960 7-F-Q —CH═CH— H H —SCH₂-Tet 961 7-F-Q —CH═CH— H H —SCH₂CH₂-Tet 962 7-F-Q —CH═CH— H H —SCH₂NHSO₂CF₃ 963 7-F-Q —CH═CH— H H —SCH₂CONHSO₂CH₃ 964 7-F-Q —CH═CH— H H —SCH₂CONHSO₂CF₃ 965 7-F-Q —CH═CH— H H —SCH₂CONHSO₂Ph 966 7-F-Q —CH═CH— H H —SCH₂CONHSO₂(2-CH₃—Ph) 967 7-F-Q —CH═CH— H H —SCH₂CH₂NHSO₂CF₃ 968 7-F-Q —CH═CH— H H —SCH₂CH₂CONHSO₂CH₃ 969 7-F-Q —CH═CH— H H —SCH₂CH₂CONHSO₂CF₃ 970 7-F-Q —CH═CH— H H —SCH₂CH₂CONHSO₂Ph 971 7-F-Q —CH═CH— H H —SCH₂CH₂CONHSO₂(2-CH₃—Ph) 972 7-F-Q —CH═CH— H H —CH₂COOH 973 7-F-Q —CH═CH— H H —CH₂CH₂COOH 974 7-F-Q —CH═CH— H H —CH₂CH₂CH₂COOH 975 7-F-Q —CH═CH— H 9-F —OCH₂COOH 976 7-F-Q —CH═CH— H 9-F —OCH(CH₃)COOH 977 7-F-Q —CH═CH— H 9-F —OCH₂CH₂COOH 978 7-F-Q —CH═CH— H 9-F —SCH₂COOH 979 7-F-Q —CH═CH— H 9-F —SCH(CH₃)COOH 980 7-F-Q —CH═CH— H 9-F —SCH₂CH₂COOH 981 7-F-Q —CH═CH— H 9-F —SCH₂CH(CH₃)COOH 982 7-F-Q —CH═CH— H 9-F —SCH₂CH(CH₂CH₃)COOH 983 7-F-Q —CH═CH— H 9-F —SCH₂C(CH₂CH₂)CH₂COOH 984 7-F-Q —CH═CH— H 8-F —OCH₂COOH 985 7-F-Q —CH═CH— H 8-F —OCH₂CH₂COOH 986 7-F-Q —CH═CH— H 8-F —SCH₂COOH 987 7-F-Q —CH═CH— H 8-F —SCH₂CH₂COOH 988 7-F-Q —CH═CH— H 8-F —SCH₂CH(CH₃)COOH 989 7-F-Q —CH═CH— H 8-F —SCH₂C(CH₂CH₂)CH₂COOH 990 7-F-Q —CH═CH— H 7-F —OCH₂COOH 991 7-F-Q —CH═CH— H 7-F —OCH₂CH₂COOH 992 7-F-Q —CH═CH— H 7-F —SCH₂COOH 993 7-F-Q —CH═CH— H 7-F —SCH₂CH₂COOH 994 7-F-Q —CH═CH— H 7-F —SCH₂CH(CH₃)COOH 995 7-F-Q —CH═CH— H 6-F —OCH₂COOH 996 7-F-Q —CH═CH— H 6-F —OCH(CH₃)COOH 997 7-F-Q —CH═CH— H 6-F —OCH₂CH₂COOH 998 7-F-Q —CH═CH— H 6-F —OCH₂CH(CH3)COOH 999 7-F-Q —CH═CH— H 6-F —OCH₂C(CH₂CH₂)CH₂COOH 1000 7-F-Q —CH═CH— H 6-F —SCH₂COOH 1001 7-F-Q —CH═CH— H 6-F —SCH(CH₃)COOH 1002 7-F-Q —CH═CH— H 6-F —SCH₂CH₂COOH 1003 7-F-Q —CH═CH— H 6-F —SCH₂CH(CH₃)COOH 1004 7-F-Q —CH═CH— H 6-F —SCH₂C(CH₂CH₂)CH₂COOH 1005 7-F-Q —CH═CH— H 9-Cl —OCH₂COOH 1006 7-F-Q —CH═CH— H 9-Cl —OCH(CH₃)COOH 1007 7-F-Q —CH═CH— H 9-Cl —OCH₂CH₂COOH 1008 7-F-Q —CH═CH— H 9-Cl —OCH₂CH(CH3)COOH 1009 7-F-Q —CH═CH— H 9-Cl —OCH₂C(CH₂CH₂)CH₂COOH 1010 7-F-Q —CH═CH— H 9-Cl —SCH₂COOH 1011 7-F-Q —CH═CH— H 9-Cl —SCH(CH₃)COOH 1012 7-F-Q —CH═CH— H 9-Cl —SCH₂CH₂COOH 1013 7-F-Q —CH═CH— H 9-Cl —SCH₂CH(CH₃)COOH 1014 7-F-Q —CH═CH— H 9-Cl —SCH₂C(CH₂CH₂)CH₂COOH 1015 7-F-Q —CH═CH— H 8-Cl —SCH₂C(CH₂CH₂)CH₂COOH 1016 7-F-Q —CH═CH— H 8-Cl —OCH₂COOH 1017 7-F-Q —CH═CH— H 8-Cl —OCH₂CH₂COOH 1018 7-F-Q —CH═CH— H 8-Cl —SCH₂COOH 1019 7-F-Q —CH═CH— H 8-Cl —SCH₂CH₂COOH 1020 7-F-Q —CH═CH— H 8-Cl —SCH₂CH(CH₃)COOH 1021 7-F-Q —CH═CH— H 7-Cl —SCH₂C(CH₂CH₂)CH₂COOH 1022 7-F-Q —CH═CH— H 7-Cl —OCH₂COOH 1023 7-F-Q —CH═CH— H 7-Cl —OCH₂CH₂COOH 1024 7-F-Q —CH═CH— H 7-Cl —SCH₂COOH 1025 7-F-Q —CH═CH— H 7-Cl —SCH₂CH₂COOH 1026 7-F-Q —CH═CH— H 7-Cl —SCH₂CH(CH₃)COOH 1027 7-F-Q —CH═CH— H 6-Cl —OCH₂COOH 1028 7-F-Q —CH═CH— H 6-Cl —OCH(CH₃)COOH 1029 7-F-Q —CH═CH— H 6-Cl —OCH₂CH₂COOH 1030 7-F-Q —CH═CH— H 6-Cl —OCH₂CH(CH3)COOH 1031 7-F-Q —CH═CH— H 6-Cl —OCH₂C(CH₂CH₂)CH₂COOH 1032 7-F-Q —CH═CH— H 6-Cl —SCH₂COOH 1033 7-F-Q —CH═CH— H 6-Cl —SCH(CH₃)COOH 1034 7-F-Q —CH═CH— H 6-Cl —SCH₂CH₂COOH 1035 7-F-Q —CH═CH— H 6-Cl —SCH₂CH(CH₃)COOH 1036 7-F-Q —CH═CH— H 6-Cl —SCH₂C(CH₂CH₂)CH₂COOH 1037 7-F-Q —CH═CH— H 9-CN —OCH₂COOH 1038 7-F-Q —CH═CH— H 9-CN —OCH(CH₃)COOH 1039 7-F-Q —CH═CH— H 9-CN —OCH₂CH₂COOH 1040 7-F-Q —CH═CH— H 9-CN —OCH₂CH(CH3)COOH 1041 7-F-Q —CH═CH— H 9-CN —OCH₂C(CH₂CH₂)CH₂COOH 1042 7-F-Q —CH═CH— H 9-CN —SCH₂COOH 1043 7-F-Q —CH═CH— H 9-CN —SCH(CH₃)COOH 1044 7-F-Q —CH═CH— H 9-CN —SCH₂CH₂COOH 1045 7-F-Q —CH═CH— H 9-CN —SCH₂CH(CH₃)COOH 1046 7-F-Q —CH═CH— H 9-CN —SCH₂C(CH₂CH₂)CH₂COOH 1047 7-F-Q —CH═CH— H 8-CN —OCH₂COOH 1048 7-F-Q —CH═CH— H 8-CN —OCH₂CH₂COOH 1049 7-F-Q —CH═CH— H 8-CN —SCH₂COOH 1050 7-F-Q —CH═CH— H 8-CN —SCH₂CH₂COOH 1051 7-F-Q —CH═CH— H 8-CN —SCH₂CH(CH₃)COOH 1052 7-F-Q —CH═CH— H 8-CN —SCH₂C(CH₂CH₂)CH₂COOH 1053 7-F-Q —CH═CH— H 7-CN —OCH₂COOH 1054 7-F-Q —CH═CH— H 7-CN —OCH₂CH₂COOH 1055 7-F-Q —CH═CH— H 7-CN —SCH₂COOH 1056 7-F-Q —CH═CH— H 7-CN —SCH₂CH₂COOH 1057 7-F-Q —CH═CH— H 7-CN —SCH₂CH(CH₃)COOH 1058 7-F-Q —CH═CH— H 9-CH₃ —OCH₂COOH 1059 7-F-Q —CH═CH— H 9-CH₃ —OCH₂CH₂COOH 1060 7-F-Q —CH═CH— H 9-CH₃ —SCH₂COOH 1061 7-F-Q —CH═CH— H 9-CH₃ —SCH₂CH₂COOH 1062 7-F-Q —CH═CH— H 9-CH₃ —SCH₂CH(CH₃)COOH 1063 7-F-Q —CH═CH— H 9-CH₃ —SCH₂CH(CH₂CH₃)COOH 1064 7-F-Q —CH═CH— H 9-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 1065 7-F-Q —CH═CH— H 8-CH₃ —OCH₂COOH 1066 7-F-Q —CH═CH— H 8-CH₃ —OCH₂CH₂COOH 1067 7-F-Q —CH═CH— H 8-CH₃ —SCH₂COOH 1068 7-F-Q —CH═CH— H 8-CH₃ —SCH₂CH₂COOH 1069 7-F-Q —CH═CH— H 8-CH₃ —SCH₂CH(CH₃)COOH 1070 7-F-Q —CH═CH— H 8-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 1071 7-F-Q —CH═CH— H 7-CH₃ —OCH₂COOH 1072 7-F-Q —CH═CH— H 7-CH₃ —OCH₂CH₂COOH 1073 7-F-Q —CH═CH— H 7-CH₃ —SCH₂COOH 1074 7-F-Q —CH═CH— H 7-CH₃ —SCH₂CH₂COOH 1075 7-F-Q —CH═CH— H 7-CH₃ —SCH₂CH(CH₃)COOH 1076 7-F-Q —CH═CH— H 9-CF₃ —OCH₂COOH 1077 7-F-Q —CH═CH— H 9-CF₃ —OCH(CH₃)COOH 1078 7-F-Q —CH═CH— H 9-CF₃ —OCH₂CH₂COOH 1079 7-F-Q —CH═CH— H 9-CF₃ —OCH₂CH(CH3)COOH 1080 7-F-Q —CH═CH— H 9-CF₃ —OCH₂C(CH₂CH₂)CH₂COOH 1081 7-F-Q —CH═CH— H 9-CF₃ —SCH₂COOH 1082 7-F-Q —CH═CH— H 9-CF₃ —SCH(CH₃)COOH 1083 7-F-Q —CH═CH— H 9-CF₃ —SCH₂CH₂COOH 1084 7-F-Q —CH═CH— H 9-CF₃ —SCH₂CH(CH₃)COOH 1085 7-F-Q —CH═CH— H 9-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 1086 7-F-Q —CH═CH— H 8-CF₃ —OCH₂COOH 1087 7-F-Q —CH═CH— H 8-CF₃ —OCH₂CH₂COOH 1088 7-F-Q —CH═CH— H 8-CF₃ —SCH₂COOH 1089 7-F-Q —CH═CH— H 8-CF₃ —SCH₂CH₂COOH 1090 7-F-Q —CH═CH— H 8-CF₃ —SCH₂CH(CH₃)COOH 1091 7-F-Q —CH═CH— H 8-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 1092 7-F-Q —CH═CH— H 7-CF₃ —OCH₂COOH 1093 7-F-Q —CH═CH— H 7-CF₃ —OCH₂CH₂COOH 1094 7-F-Q —CH═CH— H 7-CF₃ —SCH₂COOH 1095 7-F-Q —CH═CH— H 7-CF₃ —SCH₂CH₂COOH 1096 7-F-Q —CH═CH— H 7-CF₃ —SCH₂CH(CH₃)COOH 1097 7-F-Q —CH═CH— H 9-C≡CH —OCH₂COOH 1098 7-F-Q —CH═CH— H 9-C≡CH —OCH(CH₃)COOH 1099 7-F-Q —CH═CH— H 9-C≡CH —OCH₂CH₂COOH 1100 7-F-Q —CH═CH— H 9-C≡CH —OCH₂CH(CH3)COOH 1101 7-F-Q —CH═CH— H 9-C≡CH —OCH₂C(CH₂CH₂)CH₂COOH 1102 7-F-Q —CH═CH— H 9-C≡CH —SCH₂COOH 1103 7-F-Q —CH═CH— H 9-C≡CH —SCH(CH₃)COOH 1104 7-F-Q —CH═CH— H 9-C≡CH —SCH₂CH₂COOH 1105 7-F-Q —CH═CH— H 9-C≡CH —SCH₂CH(CH₃)COOH 1106 7-F-Q —CH═CH— H 9-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 1107 7-F-Q —CH═CH— H 8-C≡CH —OCH₂COOH 1108 7-F-Q —CH═CH— H 8-C≡CH —OCH₂CH₂COOH 1109 7-F-Q —CH═CH— H 8-C≡CH —SCH₂COOH 1110 7-F-Q —CH═CH— H 8-C≡CH —SCH₂CH₂COOH 1111 7-F-Q —CH═CH— H 8-C≡CH —SCH₂CH(CH₃)COOH 1112 7-F-Q —CH═CH— H 8-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 1113 7-F-Q —CH═CH— H 7-C≡CH —OCH₂COOH 1114 7-F-Q —CH═CH— H 7-C≡CH —OCH₂CH₂COOH 1115 7-F-Q —CH═CH— H 7-C≡CH —SCH₂COOH 1116 7-F-Q —CH═CH— H 7-C≡CH —SCH₂CH₂COOH 1117 7-F-Q —CH═CH— H 7-C≡CH —SCH₂CH(CH₃)COOH 1118 7-F-Q —CH═CH— H 9-CH₂OH —OCH₂COOH 1119 7-F-Q —CH═CH— H 9-CH₂OH —SCH₂CH₂COOH 1120 7-F-Q —CH═CH— H 8-CH₂OH —OCH₂COOH 1121 7-F-Q —CH═CH— H 8-CH₂OH —SCH₂CH₂COOH 1122 7-F-Q —CH═CH— H 7-CH₂OH —OCH₂COOH 1123 7-F-Q —CH═CH— H 7-CH₂OH —SCH₂CH₂COOH 1124 7-F-Q —CH═CH— H 9- —OCH₂COOH C(CH₃)₂OH 1125 7-F-Q —CH═CH— H 9- —SCH₂CH₂COOH C(CH₃)₂OH 1126 7-F-Q —CH═CH— H 8- —OCH₂COOH C(CH₃)₂OH 1127 7-F-Q —CH═CH— H 8- —SCH₂CH₂COOH C(CH₃)₂OH 1128 7-F-Q —CH═CH— H 7- —OCH₂COOH C(CH₃)₂OH 1129 7-F-Q —CH═CH— H 7- —SCH₂CH₂COOH C(CH₃)₂OH 1130 7-F-Q —CH═CH— H 9-OCH₃ —OCH₂COOH 1131 7-F-Q —CH═CH— H 9-OCH₃ —SCH₂CH₂COOH 1132 7-F-Q —CH═CH— H 8-OCH₃ —OCH₂COOH 1133 7-F-Q —CH═CH— H 8-OCH₃ —SCH₂CH₂COOH 1134 7-F-Q —CH═CH— H 7-OCH₃ —OCH₂COOH 1135 7-F-Q —CH═CH— H 7-OCH₃ —SCH₂CH₂COOH 1136 7-F-Q —CH═CH— H 9-OCHF₂ —OCH₂COOH 1137 7-F-Q —CH═CH— H 9-OCHF₂ —SCH₂CH₂COOH 1138 7-F-Q —CH═CH— H 8-OCHF₂ —OCH₂COOH 1139 7-F-Q —CH═CH— H 8-OCHF₂ —SCH₂CH₂COOH 1140 7-F-Q —CH═CH— H 7-OCHF₂ —OCH₂COOH 1141 7-F-Q —CH═CH— H 7-OCHF₂ —SCH₂CH₂COOH 1142 7-F-Q —CH═CH— H 9-OCF₃ —OCH₂COOH 1143 7-F-Q —CH═CH— H 9-OCF₃ —SCH₂CH₂COOH 1144 7-F-Q —CH═CH— H 8-OCF₃ —OCH₂COOH 1145 7-F-Q —CH═CH— H 8-OCF₃ —SCH₂CH₂COOH 1146 7-F-Q —CH═CH— H 7-OCF₃ —OCH₂COOH 1147 7-F-Q —CH═CH— H 7-OCF₃ —SCH₂CH₂COOH 1148 7-F-Q —CH═CH— H 9-SOCH₃ —OCH₂COOH 1149 7-F-Q —CH═CH— H 9-SOCH₃ —SCH₂CH₂COOH 1150 7-F-Q —CH═CH— H 8-SOCH₃ —OCH₂COOH 1151 7-F-Q —CH═CH— H 8-SOCH₃ —SCH₂CH₂COOH 1152 7-F-Q —CH═CH— H 7-SOCH₃ —OCH₂COOH 1153 7-F-Q —CH═CH— H 7-SOCH₃ —SCH₂CH₂COOH 1154 7-F-Q —CH═CH— H 9-SO₂CH₃ —OCH₂COOH 1155 7-F-Q —CH═CH— H 9-SO₂CH₃ —SCH₂CH₂COOH 1156 7-F-Q —CH═CH— H 8-SO₂CH₃ —OCH₂COOH 1157 7-F-Q —CH═CH— H 8-SO₂CH₃ —SCH₂CH₂COOH 1158 7-F-Q —CH═CH— H 7-SO₂CH₃ —OCH₂COOH 1159 7-F-Q —CH═CH— H 7-SO₂CH₃ —SCH₂CH₂COOH 1160 7-F-Q —CH═CH— H 9-CH═CH₂ —SCH₂CH₂COOH 1161 7-F-Q —CH═CH— H 8-CH═CH₂ —SCH₂CH₂COOH 1162 7-F-Q —CH═CH— H 7-CH═CH₂ —SCH₂CH₂COOH 1163 7-F-Q —CH═CH— H 9-NO₂ —OCH₂COOH 1164 7-F-Q —CH═CH— H 9-NO₂ —SCH₂OH₂COOH 1165 7-F-Q —CH═CH— H 8-NO₂ —OCH₂COOH 1166 7-F-Q —CH═CH— H 8-NO₂ —SCH₂CH₂COOH 1167 7-F-Q —CH═CH— H 7-NO₂ —OCH₂COOH 1168 7-F-Q —CH═CH— H 7-NO₂ —SCH₂CH₂COOH 1169 7-F-Q —CH═CH— 1-F H —SCH₂CH₂COOH 1170 7-F-Q —CH═CH— 2-F H —SCH₂CH₂COOH 1171 7-F-Q —CH═CH— 1-Cl H —SCH₂CH₂COOH 1172 7-F-Q —CH═CH— 2-Cl H —SCH₂CH₂COOH 1173 7-F-Q —CH═CH— 1-CH₃ H —SCH₂CH₂COOH 1174 7-F-Q —CH═CH— 2-CH₃ H —SCH₂CH₂COOH 1175 7-F-Q —CH═CH— 1-OCH₃ H —SCH₂CH₂COOH 1176 7-F-Q —CH═CH— 2-OCH₃ H —SCH₂CH₂COOH 1177 7-F-Q —CH═CH— 1-NO₂ H —SCH₂CH₂COOH 1178 7-F-Q —CH═CH— 2-NO₂ H —SCH₂CH₂COOH 1179 7-F-Q —CH═CH— 1-CN H —SCH₂CH₂COOH 1180 7-F-Q —CH═CH— 2-CN H —SCH₂CH₂COOH 1181 7-F-Q —CH₂O— H H —OCH₂COOH 1182 7-F-Q —CH₂O— H H —OCH(CH3)COOH 1183 7-F-Q —CH₂O— H H —OCH₂CH₂COOH 1184 7-F-Q —CH₂O— H H —OCH₂CH(CH₃)COOH 1185 7-F-Q —CH₂O— H H —OCH₂C(CH₂CH₂)CH₂COOH 1186 7-F-Q —CH₂O— H H —SCH₂COOH 1187 7-F-Q —CH₂O— H H —SCH(CH3)COOH 1188 7-F-Q —CH₂O— H H —SCH₂CH₂COOH 1189 7-F-Q —CH₂O— H H —SCH₂CH(CH₃)COOH 1190 7-F-Q —CH₂O— H H —SCH₂C(CH₃)₂COOH 1191 7-F-Q —CH₂O— H H —SCH₂CH(CH₂CH₃)COOH 1192 7-F-Q —CH₂O— H H —SCH(CH₃)CH₂COOH 1193 7-F-Q —CH₂O— H H —SO(CH₃)₂CH₂COOH 1194 7-F-Q —CH₂O— H H —SCH₂CH₂CH₂COOH 1195 7-F-Q —CH₂O— H H —SCH₂CH(CH₃)CH₂COOH 1196 7-F-Q —CH₂O— H H —SCH₂C(CH₃)₂CH₂COOH 1197 7-F-Q —CH₂O— H H —SCH₂C(CH₂CH₂)CH₂COOH 1198 7-F-Q —CH₂O— H H —SCH₂CF₂COOH 1199 7-F-Q —CH₂O— H H —SCH₂CF₂CH₂COOH 1200 7-F-Q —CH₂O— H H —SCH₂-Tet 1201 7-F-Q —CH₂O— H H —SCH₂CH₂-Tet 1202 7-F-Q —CH₂O— H H —SCH₂NHSO₂CF₃ 1203 7-F-Q —CH₂O— H H —SCH₂CONHSO₂CH₃ 1204 7-F-Q —CH₂O— H H —SCH₂CONHSO₂CF₃ 1205 7-F-Q —CH₂O— H H —SCH₂CONHSO₂Ph 1206 7-F-Q —CH₂O— H H —SCH₂CONHSO₂(2-CH₃—Ph) 1207 7-F-Q —CH₂O— H H —SCH₂CH₂NHSO₂CF₃ 1208 7-F-Q —CH₂O— H H —SCH₂CH₂CONHSO₂CH₃ 1209 7-F-Q —CH₂O— H H —SCH₂CH₂CONHSO₂CF₃ 1210 7-F-Q —CH₂O— H H —SCH₂CH₂CONHSO₂Ph 1211 7-F-Q —CH₂O— H H —SCH₂CH₂CONHSO₂(2-CH₃—Ph) 1212 7-F-Q —CH₂O— H H —CH₂COOH 1213 7-F-Q —CH₂O— H H —CH₂CH₂COOH 1214 7-F-Q —CH₂O— H H —CH₂CH₂CH₂COOH 1215 7-F-Q —CH₂O— H 9-F —OCH₂COOH 1216 7-F-Q —CH₂O— H 9-F —OCH(CH₃)COOH 1217 7-F-Q —CH₂O— H 9-F —OCH₂CH₂COOH 1218 7-F-Q —CH₂O— H 9-F —OCH₂CH(CH3)COOH 1219 7-F-Q —CH₂O— H 9-F —OCH₂C(CH₂CH₂)CH₂COOH 1220 7-F-Q —CH₂O— H 9-F —SCH₂COOH 1221 7-F-Q —CH₂O— H 9-F —SCH(CH₃)COOH 1222 7-F-Q —CH₂O— H 9-F —SCH₂CH₂COOH 1223 7-F-Q —CH₂O— H 9-F —SCH₂CH(CH₃)COOH 1224 7-F-Q —CH₂O— H 9-F —SCH₂C(CH₂CH₂)CH₂COOH 1225 7-F-Q —CH₂O— H 8-F —OCH₂COOH 1226 7-F-Q —CH₂O— H 8-F —OCH₂CH₂COOH 1227 7-F-Q —CH₂O— H 8-F —SCH₂COOH 1228 7-F-Q —CH₂O— H 8-F —SCH₂CH₂COOH 1229 7-F-Q —CH₂O— H 8-F —SCH₂CH(CH₃)COOH 1230 7-F-Q —CH₂O— H 8-F —SCH₂C(CH₂CH₂)CH₂COOH 1231 7-F-Q —CH₂O— H 7-F —OCH₂COOH 1232 7-F-Q —CH₂O— H 7-F —OCH₂CH₂COOH 1233 7-F-Q —CH₂O— H 7-F —SCH₂COOH 1234 7-F-Q —CH₂O— H 7-F —SCH₂CH₂COOH 1235 7-F-Q —CH₂O— H 7-F —SCH₂CH(CH₃)COOH 1236 7-F-Q —CH₂O— H 6-F —OCH₂COOH 1237 7-F-Q —CH₂O— H 6-F —OCH(CH₃)COOH 1238 7-F-Q —CH₂O— H 6-F —OCH₂CH₂COOH 1239 7-F-Q —CH₂O— H 8-F —OCH₂CH(CH₃)COOH 1240 7-F-Q —CH₂O— H 6-F —OCH₂C(CH₂CH₂)CH₂COOH 1241 7-F-Q —CH₂O— H 6-F —SCH₂COOH 1242 7-F-Q —CH₂O— H 6-F —SCH(CH₃)COOH 1243 7-F-Q —CH₂O— H 6-F —SCH₂CH₂COOH 1244 7-F-Q —CH₂O— H 6-F —SCH₂CH(CH₃)COOH 1245 7-F-Q —CH₂O— H 6-F —SCH₂C(CH₂CH₂)CH₂COOH 1246 7-F-Q —CH₂O— H 9-Cl —OCH₂COOH 1247 7-F-Q —CH₂O— H 9-Cl —OCH(CH₃)COOH 1248 7-F-Q —CH₂O— H 9-Cl —OCH₂CH₂COOH 1249 7-F-Q —CH₂O— H 9-Cl —OCH₂CH(CH3)COOH 1250 7-F-Q —CH₂O— H 9-Cl —OCH₂C(CH₂CH₂)CH₂COOH 1251 7-F-Q —CH₂O— H 9-Cl —SCH₂COOH 1252 7-F-Q —CH₂O— H 9-Cl —SCH(CH₃)COOH 1253 7-F-Q —CH₂O— H 9-Cl —SCH₂CH₂COOH 1254 7-F-Q —CH₂O— H 9-Cl —SCH₂CH(CH₃)COOH 1255 7-F-Q —CH₂O— H 9-Cl —SCH₂C(CH₂CH₂)CH₂COOH 1256 7-F-Q —CH₂O— H 8-Cl —SCH₂C(CH₂CH₂)CH₂COOH 1257 7-F-Q —CH₂O— H 8-Cl —OCH₂COOH 1258 7-F-Q —CH₂O— H 8-Cl —OCH₂CH₂COOH 1259 7-F-Q —CH₂O— H 8-Cl —SCH₂COOH 1260 7-F-Q —CH₂O— H 8-Cl —SCH₂CH₂COOH 1261 7-F-Q —CH₂O— H 8-Cl —SCH₂CH(CH₃)COOH 1295 7-F-Q —CH₂O— H 8-CH₃ —OCH₂COOH 1296 7-F-Q —CH₂O— H 8-CH₃ —OCH₂CH₂COOH 1297 7-F-Q —CH₂O— H 8-CH₃ —SCH₂COOH 1298 7-F-Q —CH₂O— H 8-CH₃ —SCH₂CH₂COOH 1299 7-F-Q —CH₂O— H 8-CH₃ —SCH₂CH(CH₃)COOH 1300 7-F-Q —CH₂O— H 8-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 1301 7-F-Q —CH₂O— H 7-CH₃ —OCH₂COOH 1302 7-F-Q —CH₂O— H 7-CH₃ —OCH₂CH₂COOH 1303 7-F-Q —CH₂O— H 7-CH₃ —SCH₂COOH 1304 7-F-Q —CH₂O— H 7-CH₃ —SCH₂CH₂COOH 1305 7-F-Q —CH₂O— H 7-CH₃ —SCH₂CH(CH₃)COOH 1306 7-F-Q —CH₂O— H 9-CF₃ —OCH₂COOH 1307 7-F-Q —CH₂O— H 9-CF₃ —OCH(CH₃)COOH 1308 7-F-Q —CH₂O— H 9-CF₃ —OCH₂CH₂COOH 1309 7-F-Q —CH₂O— H 9-CF₃ —OCH₂CH(CH3)COOH 1310 7-F-Q —CH₂O— H 9-CF₃ —OCH₂C(CH₂CH₂)CH₂COOH 1311 7-F-Q —CH₂O— H 9-CF₃ —SCH₂COOH 1312 7-F-Q —CH₂O— H 9-CF₃ —SCH(CH₃)COOH 1313 7-F-Q —CH₂O— H 9-CF₃ —SCH₂CH₂COOH 1314 7-F-Q —CH₂O— H 9-CF₃ —SCH₂CH(CH₃)COOH 1315 7-F-Q —CH₂O— H 9-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 1316 7-F-Q —CH₂O— H 8-CF₃ —OCH₂COOH 1317 7-F-Q —CH₂O— H 8-CF₃ —OCH₂CH₂COOH 1318 7-F-Q —CH₂O— H 8-CF₃ —SCH₂COOH 1319 7-F-Q —CH₂O— H 8-CF₃ —SCH₂CH₂COOH 1320 7-F-Q —CH₂O— H 8-CF₃ —SCH₂CH(CH₃)COOH 1321 7-F-Q —CH₂O— H 8-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 1322 7-F-Q —CH₂O— H 7-CF₃ —OCH₂COOH 1323 7-F-Q —CH₂O— H 7-CF₃ —OCH₂CH₂COOH 1324 7-F-Q —CH₂O— H 7-CF₃ —SCH₂COOH 1325 7-F-Q —CH₂O— H 7-CF₃ —SCH₂CH₂COOH 1326 7-F-Q —CH₂O— H 7-CF₃ —SCH₂CH(CH₃)COOH 1327 7-F-Q —CH₂O— H 9-C≡CH —OCH₂COOH 1328 7-F-Q —CH₂O— H 9-C≡CH —OCH(CH₃)COOH 1329 7-F-Q —CH₂O— H 9-C≡CH —OCH₂CH₂COOH 1330 7-F-Q —CH₂O— H 9-C≡CH —OCH₂CH(CH3)COOH 1331 7-F-Q —CH₂O— H 9-C≡CH —OCH₂C(CH₂CH₂)CH₂COOH 1332 7-F-Q —CH₂O— H 9-C≡CH —SCH₂COOH 1333 7-F-Q —CH₂O— H 9-C≡CH —SCH(CH₃)COOH 1334 7-F-Q —CH₂O— H 9-C≡CH —SCH₂CH₂COOH 1335 7-F-Q —CH₂O— H 9-C≡CH —SCH₂CH(CH₃)COOH 1336 7-F-Q —CH₂O— H 9-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 1337 7-F-Q —CH₂O— H 8-C≡CH —OCH₂COOH 1338 7-F-Q —CH₂O— H 8-C≡CH —OCH₂CH₂COOH 1339 7-F-Q —CH₂O— H 8-C≡CH —SCH₂COOH 1340 7-F-Q —CH₂O— H 8-C≡CH —SCH₂CH₂COOH 1341 7-F-Q —CH₂O— H 8-C≡CH —SCH₂CH(CH₃)COOH 1342 7-F-Q —CH₂O— H 8-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 1343 7-F-Q —CH₂O— H 7-C≡CH —OCH₂COOH 1344 7-F-Q —CH₂O— H 7-C≡CH —OCH₂CH₂COOH 1345 7-F-Q —CH₂O— H 7-C≡CH —SCH₂COOH 1346 7-F-Q —CH₂O— H 7-C≡CH —SCH₂CH₂COOH 1347 7-F-Q —CH₂O— H 7-C≡CH —SCH₂CH(CH₃)COOH 1348 7-F-Q —CH₂O— H 9-CH₂OH —OCH₂COOH 1349 7-F-Q —CH₂O— H 9-CH₂OH —SCH₂CH₂COOH 1350 7-F-Q —CH₂O— H 8-CH₂OH —OCH₂COOH 1351 7-F-Q —CH₂O— H 8-CH₂OH —SCH₂CH₂COOH 1352 7-F-Q —CH₂O— H 7-CH₂OH —OCH₂COOH 1353 7-F-Q —CH₂O— H 7-CH₂OH —SCH₂CH₂COOH 1354 7-F-Q —CH₂O— H 9- —OCH₂COOH C(CH₃)₂OH 1355 7-F-Q —CH₂O— H 9- —SCH₂CH₂COOH C(CH₃)₂OH 1356 7-F-Q —CH₂O— H 8- —OCH₂COOH C(CH₃)₂OH 1357 7-F-Q —CH₂O— H 8- —SCH₂CH₂COOH C(CH₃)₂OH 1358 7-F-Q —CH₂O— H 7- —OCH₂COOH C(CH₃)₂OH 1359 7-F-Q —CH₂O— H 7- —SCH₂CH₂COOH C(CH₃)₂OH 1360 7-F-Q —CH₂O— H 9-OCH₃ —OCH₂COOH 1361 7-F-Q —CH₂O— H 9-OCH₃ —SCH₂CH₂COOH 1362 7-F-Q —CH₂O— H 8-OCH₃ —OCH₂COOH 1363 7-F-Q —CH₂O— H 8-OCH₃ —SCH₂CH₂COOH 1364 7-F-Q —CH₂O— H 7-OCH₃ —OCH₂COOH 1365 7-F-Q —CH₂O— H 7-OCH₃ —SCH₂CH₂COOH 1366 7-F-Q —CH₂O— H 9-OCHF₂ —OCH₂COOH 1367 7-F-Q —CH₂O— H 9-OCHF₂ —SCH₂CH₂COOH 1368 7-F-Q —CH₂O— H 8-OCHF₂ —OCH₂COOH 1369 7-F-Q —CH₂O— H 8-COHF₂ —SCH₂CH₂COOH 1370 7-F-Q —CH₂O— H 7-OCHF₂ —OCH₂COOH 1371 7-F-Q —CH₂O— H 7-OCHF₂ —SCH₂CH₂COOH 1372 7-F-Q —CH₂O— H 9-OCF₃ —OCH₂COOH 1373 7-F-Q —CH₂O— H 9-OCF₃ —SCH₂CH₂COOH 1374 7-F-Q —CH₂O— H 8-OCF₃ —OCH₂COOH 1375 7-F-Q —CH₂O— H 8-OCF₃ —SCH₂CH₂COOH 1376 7-F-Q —CH₂O— H 7-OCF₃ —OCH₂COOH 1377 7-F-Q —CH₂O— H 7-OCF₃ —SCH₂CH₂COOH 1378 7-F-Q —CH₂O— H 9-SOCH₃ —OCH₂COOH 1379 7-F-Q —CH₂O— H 9-SOCH₃ —SCH₂CH₂COOH 1380 7-F-Q —CH₂O— H 8-SOCH₃ —OCH₂COOH 1381 7-F-Q —CH₂O— H 8-SOCH₃ —SCH₂CH₂COOH 1382 7-F-Q —CH₂O— H 7-SOCH₃ —OCH₂COOH 1383 7-F-Q —CH₂O— H 7-SOCH₃ —SCH₂CH₂COOH 1384 7-F-Q —CH₂O— H 9-SO₂CH₃ —OCH₂COOH 1385 7-F-Q —CH₂O— H 9-SO₂CH₃ —SCH₂CH₂COOH 1386 7-F-Q —CH₂O— H 8-SO₂CH₃ —OCH₂COOH 1387 7-F-Q —CH₂O— H 8-SO₂CH₃ —SCH₂CH₂COOH 1388 7-F-Q —CH₂O— H 7-SO₂CH₃ —OCH₂COOH 1389 7-F-Q —CH₂O— H 7-SO₂CH₃ —SCH₂CH₂COOH 1390 7-F-Q —CH₂O— H 9-CH═CH₂ —SCH₂CH₂COOH 1391 7-F-Q —CH₂O— H 8-CH═CH₂ —SCH₂CH₂COOH 1392 7-F-Q —CH₂O— H 7-CH═CH₂ —SCH₂CH₂COOH 1393 7-F-Q —CH₂O— H 9-NO₂ —OCH₂COOH 1394 7-F-Q —CH₂O— H 9-NO₂ —SCH₂CH₂COOH 1395 7-F-Q —CH₂O— H 8-NO₂ —OCH₂COOH 1396 7-F-Q —CH₂O— H 8-NO₂ —SCH₂CH₂COOH 1397 7-F-Q —CH₂O— H 7-NO₂ —OCH₂COOH 1398 7-F-Q —CH₂O— H 7-NO₂ —SCH₂CH₂COOH 1399 7-F-Q —CH₂O— 1-F H —SCH₂CH₂COOH 1400 7-F-Q —CH₂O— 2-F H —SCH₂CH₂COOH 1401 7-F-Q —CH₂O— 1-Cl H —SCH₂CH₂COOH 1402 7-F-Q —CH₂O— 2-Cl H —SCH₂CH₂COOH 1403 7-F-Q —CH₂O— 1-CH₃ H —SCH₂CH₂COOH 1404 7-F-Q —CH₂O— 2-CH₃ H —SCH₂CH₂COOH 1405 7-F-Q —CH₂O— 1-OCH₃ H —SCH₂CH₂COOH 1406 7-F-Q —CH₂O— 2-OCH₃ H —SCH₂CH₂COOH 1407 7-F-Q —CH₂O— 1-NO₂ H —SCH₂CH₂COOH 1408 7-F-Q —CH₂O— 2-NO₂ H —SCH₂CH₂COOH 1409 7-F-Q —CH₂O— 1-CN H —SCH₂CH₂COOH 1410 7-F-Q —CH₂O— 2-CN H —SCH₂CH₂COOH 1411 7-Cl-Q —CH═CH— H H —OCH₂COOH 1412 7-Cl-Q —CH═CH— H H —OCH(CH₃)COOH 1413 7-Cl-Q —CH═CH— H H —OCH₂CH₂COOH 1414 7-Cl-Q —CH═CH— H H —OCH₂CH(CH₃)COOH 1415 7-Cl-Q —CH═CH— H H —OCH₂C(CH₂CH₂)CH₂COOH 1416 7-Cl-Q —CH═CH— H H —SCH₂COOH 1417 7-Cl-Q —CH═CH— H H —SCH(CH₃)COOH 1418 7-Cl-Q —CH═CH— H H —SCH₂CH₂COOH 1419 7-Cl-Q —CH═CH— H H —SCH₂CH(CH₃)COOH 1420 7-Cl-Q —CH═CH— H H —SCH₂C(CH₃)₂COOH 1421 7-Cl-Q —CH═CH— H H —SCH₂CH(CH₂CH₃)COOH 1422 7-Cl-Q —CH═CH— H H —SCH(CH₃)CH₂COOH 1423 7-Cl-Q —CH═CH— H H —SC(CH₃)₂CH₂COOH 1424 7-Cl-Q —CH═CH— H H —SCH₂CH₂CH₂COOH 1425 7-Cl-Q —CH═CH— H H —SCH₂CH(CH₃)CH₂COOH 1426 7-Cl-Q —CH═CH— H H —SCH₂C(CH₃)₂CH₂COOH 1427 7-Cl-Q —CH═CH— H H —SCH₂C(CH₂CH₂)CH₂COOH 1428 7-Cl-Q —CH═CH— H H —SCH₂CF₂COOH 1429 7-Cl-Q —CH═CH— H H —SCH₂CF₂CH₂COOH 1430 7-Cl-Q —CH═CH— H H —SCH₂-Tet 1431 7-Cl-Q —CH═CH— H H —SCH₂CH₂-Tet 1432 7-Cl-Q —CH═CH— H H —SCH₂NHSO₂CF₃ 1433 7-Cl-Q —CH═CH— H H —SCH₂CONHSO₂CH₃ 1434 7-Cl-Q —CH═CH— H H —SCH₂CONHSO₂CF₃ 1435 7-Cl-Q —CH═CH— H H —SCH₂CONHSO₂Ph 1436 7-Cl-Q —CH═CH— H H —SCH₂CONHSO₂(2-CH₃—Ph) 1437 7-Cl-Q —CH═CH— H H —SCH₂CH₂NHSO₂CF₃ 1438 7-Cl-Q —CH═CH— H H —SCH₂CH₂CONHSO₂CH₃ 1439 7-Cl-Q —CH═CH— H H —SCH₂CH₂CONHSO₂CF₃ 1440 7-Cl-Q —CH═CH— H H —SCH₂CH₂CONHSO₂Ph 1441 7-Cl-Q —CH═CH— H H —SCH₂CH₂CONHSO₂(2-CH₃—Ph) 1442 7-Cl-Q —CH═CH— H H —CH₂COOH 1443 7-Cl-Q —CH═CH— H H —CH₂CH₂COOH 1444 7-Cl-Q —CH═CH— H H —CH₂CH₂CH₂COOH 1445 7-Cl-Q —CH═CH— H 9-F —OCH₂COOH 1446 7-Cl-Q —CH═CH— H 9-F —OCH(CH₃)COOH 1447 7-Cl-Q —CH═CH— H 9-F —OCH₂CH₂COOH 1448 7-Cl-Q —OH═CH— H 9-F —SCH₂COOH 1449 7-Cl-Q —CH═CH— H 9-F —SCH(CH₃)COOH 1450 7-Cl-Q —CH═CH— H 9-F —SCH₂CH₂COOH 1451 7-Cl-Q —CH═CH— H 9-F —SCH₂CH(CH₃)COOH 1452 7-Cl-Q —CH═CH— H 9-F —SCH₂CH(CH₂CH₃)COOH 1453 7-Cl-Q —CH═CH— H 9-F —SCH₂C(CH₂CH₂)CH₂COOH 1454 7-Cl-Q —CH═CH— H 8-F —OCH₂COOH 1455 7-Cl-Q —CH═CH— H 8-F —OCH₂CH₂COOH 1456 7-Cl-Q —CH═CH— H 8-F —SCH₂COOH 1457 7-Cl-Q —CH═CH— H 8-F —SCH₂CH₂COOH 1458 7-Cl-Q —CH═CH— H 8-F —SCH₂CH(CH₃)COOH 1459 7-Cl-Q —CH═CH— H 8-F —SCH₂C(CH₂CH₂)CH₂COOH 1460 7-Cl-Q —CH═CH— H 7-F —OCH₂COOH 1461 7-Cl-Q —CH═CH— H 7-F —OCH₂CH₂COOH 1462 7-Cl-Q —CH═CH— H 7-F —SCH₂COOH 1463 7-Cl-Q —CH═CH— H 7-F —SCH₂CH₂COOH 1464 7-Cl-Q —CH═CH— H 7-F —SCH₂CH(CH₃)COOH 1465 7-Cl-Q —CH═CH— H 6-F —OCH₂COOH 1466 7-Cl-Q —CH═CH— H 6-F —OCH(CH₃)COOH 1467 7-Cl-Q —CH═CH— H 6-F —OCH₂CH₂COOH 1468 7-Cl-Q —CH═CH— H 6-F —OCH₂CH(CH3)COOH 1469 7-Cl-Q —CH═CH— H 6-F —OCH₂C(CH₂CH₂)CH₂COOH 1470 7-Cl-Q —CH═CH— H 6-F —SCH₂COOH 1471 7-Cl-Q —CH═CH— H 6-F —SCH(CH₃)COOH 1472 7-Cl-Q —CH═CH— H 6-F —SCH₂CH₂COOH 1473 7-Cl-Q —CH═CH— H 6-F —SCH₂CH(CH₃)COOH 1474 7-Cl-Q —CH═CH— H 6-F —SCH₂C(CH₂CH₂)CH₂COOH 1475 7-Cl-Q —CH═CH— H 9-Cl —OCH₂COOH 1476 7-Cl-Q —CH═CH— H 9-Cl —OCH(CH₃)COOH 1477 7-Cl-Q —CH═CH— H 9-Cl —OCH₂CH₂COOH 1478 7-Cl-Q —CH═CH— H 9-Cl —OCH₂CH(CH3)COOH 1479 7-Cl-Q —CH═CH— H 9-Cl —OCH₂C(CH₂CH₂)CH₂COOH 1480 7-Cl-Q —CH═CH— H 9-Cl —SCH₂COOH 1481 7-Cl-Q —CH═CH— H 9-Cl —SCH(CH₃)COOH 1482 7-Cl-Q —CH═CH— H 9-Cl —SCH₂CH₂COOH 1483 7-Cl-Q —CH═CH— H 9-Cl —SCH₂CH(CH₃)COOH 1484 7-Cl-Q —CH═CH— H 9-Cl —SCH₂C(CH₂CH₂)CH₂COOH 1485 7-Cl-Q —CH═CH— H 8-Cl —SCH₂C(CH₂CH₂)CH₂COOH 1486 7-Cl-Q —CH═CH— H 8-Cl —OCH₂COOH 1487 7-Cl-Q —CH═CH— H 8-Cl —OCH₂CH₂COOH 1488 7-Cl-Q —CH═CH— H 8-Cl —SCH₂COOH 1489 7-Cl-Q —CH═CH— H 8-Cl —SCH₂CH₂COOH 1490 7-Cl-Q —CH═CH— H 8-Cl —SCH₂CH(CH₃)COOH 1491 7-Cl-Q —CH═CH— H 7-Cl —SCH₂C(CH₂CH₂)CH₂COOH 1492 7-Cl-Q —CH═CH— H 7-Cl —OCH₂COOH 1493 7-Cl-Q —CH═CH— H 7-Cl —OCH₂CH₂COOH 1494 7-Cl-Q —CH═CH— H 7-Cl —SCH₂COOH 1495 7-Cl-Q —CH═CH— H 7-Cl —SCH₂CH₂COOH 1496 7-Cl-Q —CH═CH— H 7-Cl —SCH₂CH(CH₃)COOH 1497 7-Cl-Q —CH═CH— H 6-Cl —OCH₂COOH 1498 7-Cl-Q —CH═CH— H 6-Cl —OCH(CH₃)COOH 1499 7-Cl-Q —CH═CH— H 6-Cl —OCH₂CH₂COOH 1500 7-Cl-Q —CH═CH— H 6-Cl —OCH₂CH(CH3)COOH 1501 7-Cl-Q —CH═CH— H 6-Cl —OCH₂C(CH₂CH₂)CH₂COOH 1502 7-Cl-Q —CH═CH— H 6-Cl —SCH₂COOH 1503 7-Cl-Q —CH═CH— H 6-Cl —SCH(CH₃)COOH 1504 7-Cl-Q —CH═CH— H 6-Cl —SCH₂CH₂COOH 1505 7-Cl-Q —CH═CH— H 6-Cl —SCH₂CH(CH₃)COOH 1506 7-Cl-Q —CH═CH— H 6-Cl —SCH₂C(CH₂CH₂)CH₂COOH 1507 7-Cl-Q —CH═CH— H 9-CN —OCH₂COOH 1508 7-Cl-Q —CH═CH— H 9-CN —OCH(CH₃)COOH 1509 7-Cl-Q —CH═CH— H 9-CN —OCH₂CH₂COOH 1510 7-Cl-Q —CH═CH— H 9-CN —OCH₂CH(CH₃)COOH 1511 7-Cl-Q —CH═CH— H 9-CN —OCH₂C(CH₂CH₂)CH₂COOH 1512 7-Cl-Q —CH═CH— H 9-CN —SCH₂COOH 1513 7-Cl-Q —CH═CH— H 9-CN —SCH(CH₃)COOH 1514 7-Cl-Q —CH═CH— H 9-CN —SCH₂CH₂COOH 1515 7-Cl-Q —CH═CH— H 9-CN —SCH₂CH(CH₃)COOH 1516 7-Cl-Q —CH═CH— H 9-CN —SCH₂C(CH₂CH₂)CH₂COOH 1517 7-Cl-Q —CH═CH— H 8-CN —OCH₂COOH 1518 7-Cl-Q —CH═CH— H 8-CN —OCH₂CH₂COOH 1519 7-Cl-Q —CH═CH— H 8-CN —SCH₂COOH 1520 7-Cl-Q —CH═CH— H 8-CN —SCH₂CH₂COOH 1521 7-Cl-Q —CH═CH— H 8-CN —SCH₂CH(CH₃)COOH 1522 7-Cl-Q —CH═CH— H 8-CN —SCH₂C(CH₂CH₂)CH₂COOH 1523 7-Cl-Q —CH═CH— H 7-CN —OCH₂COOH 1524 7-Cl-Q —CH═CH— H 7-CN —OCH₂CH₂COOH 1525 7-Cl-Q —CH═CH— H 7-CN —SCH₂COOH 1526 7-Cl-Q —CH═CH— H 7-CN —SCH₂CH₂COOH 1527 7-Cl-Q —CH═CH— H 7-CN —SCH₂CH(CH₃)COOH 1528 7-Cl-Q —CH═CH— H 9-CH₃ —OCH₂COOH 1529 7-Cl-Q —CH═CH— H 9-CH₃ —OCH₂CH₂COOH 1530 7-Cl-Q —CH═CH— H 9-CH₃ —SCH₂COOH 1531 7-Cl-Q —CH═CH— H 9-CH₃ —SCH₂CH₂COOH 1532 7-Cl-Q —CH═CH— H 9-CH₃ —SCH₂CH(CH₃)COOH 1533 7-Cl-Q —CH═CH— H 9-CH₃ —SCH₂CH(CH₂CH₃)COOH 1534 7-Cl-Q —CH═CH— H 9-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 1535 7-Cl-Q —CH═CH— H 8-CH₃ —OCH₂COOH 1536 7-Cl-Q —CH═CH— H 8-CH₃ —OCH₂CH₂COOH 1537 7-Cl-Q —CH═CH— H 8-CH₃ —SCH₂COOH 1538 7-Cl-Q —CH═CH— H 8-CH₃ —SCH₂CH₂COOH 1539 7-Cl-Q —CH═CH— H 8-CH₃ —SCH₂CH(CH₃)COOH 1540 7-Cl-Q —CH═CH— H 8-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 1541 7-Cl-Q —CH═CH— H 7-CH₃ —OCH₂COOH 1542 7-Cl-Q —CH═CH— H 7-CH₃ —OCH₂CH₂COOH 1543 7-Cl-Q —CH═CH— H 7-CH₃ —SCH₂COOH 1544 7-Cl-Q —CH═CH— H 7-CH₃ —SCH₂CH₂COOH 1545 7-Cl-Q —CH═CH— H 7-CH₃ —SCH₂CH(CH₃)COOH 1546 7-Cl-Q —CH═CH— H 9-CF₃ —OCH₂COOH 1547 7-Cl-Q —CH═CH— H 9-CF₃ —OCH(CH₃)COOH 1548 7-Cl-Q —CH═CH— H 9-CF₃ —OCH₂CH₂COOH 1549 7-Cl-Q —CH═CH— H 9-CF₃ —OCH₂CH(CH3)COOH 1550 7-Cl-Q —CH═CH— H 9-CF₃ —OCH₂C(CH₂CH₂)CH₂COOH 1551 7-Cl-Q —CH═CH— H 9-CF₃ —SCH₂COOH 1552 7-Cl-Q —CH═CH— H 9-CF₃ —SCH(CH₃)COOH 1553 7-Cl-Q —CH═CH— H 9-CF₃ —SCH₂CH₂COOH 1554 7-Cl-Q —CH═CH— H 9-CF₃ —SCH₂CH(CH₃)COOH 1555 7-Cl-Q —CH═CH— H 9-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 1556 7-Cl-Q —CH═CH— H 8-CF₂ —OCH₂COOH 1557 7-Cl-Q —CH═CH— H 8-CF₃ —OCH₂CH₂COOH 1558 7-Cl-Q —CH═CH— H 8-CF₃ —SCH₂COOH 1559 7-Cl-Q —CH═CH— H 8-CF₃ —SCH₂CH₂COOH 1560 7-Cl-Q —CH═CH— H 8-CF₃ —SCH₂CH(CH₃)COOH 1561 7-Cl-Q —CH═CH— H 8-CF₃ —SCH₂C(CH₂CH₂)CH₂COOH 1562 7-Cl-Q —CH═CH— H 7-CF₃ —OCH₂COOH 1563 7-Cl-Q —CH═CH— H 7-CF₃ —OCH₂CH₂COOH 1564 7-Cl-Q —CH═CH— H 7-CF₃ —SCH₂COOH 1565 7-Cl-Q —CH═CH— H 7-CF₃ —SCH₂CH₂COOH 1566 7-Cl-Q —CH═CH— H 7-CF₃ —SCH₂CH(CH₃)COOH 1567 7-Cl-Q —CH═CH— H 9-C≡CH —OCH₂COOH 1568 7-Cl-Q —CH═CH— H 9-C≡CH —OCH(CH₃)COOH 1569 7-Cl-Q —CH═CH— H 9-C≡CH —OCH₂CH₂COOH 1570 7-Cl-Q —CH═CH— H 9-C≡CH —OCH₂CH(CH3)COOH 1571 7-Cl-Q —CH═CH— H 9-C≡CH —OCH₂C(CH₂CH₂)CH₂COOH 1572 7-Cl-Q —CH═CH— H 9-C≡CH —SCH₂COOH 1573 7-Cl-Q —CH═CH— H 9-C≡CH —SCH(CH₃)COOH 1574 7-Cl-Q —CH═CH— H 9-C≡CH —SCH₂CH₂COOH 1575 7-Cl-Q —CH═CH— H 9-C≡CH —SCH₂CH(CH₃)COOH 1576 7-Cl-Q —CH═CH— H 9-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 1577 7-Cl-Q —CH═CH— H 8-C≡CH —OCH₂COOH 1578 7-Cl-Q —CH═CH— H 8-C≡CH —OCH₂CH₂COOH 1579 7-Cl-Q —CH═CH— H 8-C≡CH —SCH₂COOH 1580 7-Cl-Q —CH═CH— H 8-C≡CH —SCH₂CH₂COOH 1581 7-Cl-Q —CH═CH— H 8-C≡CH —SCH₂CH(CH₃)COOH 1582 7-Cl-Q —CH═CH— H 8-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 1583 7-Cl-Q —CH═CH— H 7-C≡CH —OCH₂COOH 1584 7-Cl-Q —CH═CH— H 7-C≡CH —OCH₂CH₂COOH 1585 7-Cl-Q —CH═CH— H 7-C≡CH —SCH₂COOH 1586 7-Cl-Q —CH═CH— H 7-C≡CH —SCH₂CH₂COOH 1587 7-Cl-Q —CH═CH— H 7-C≡CH —SCH₂CH(CH₃)COOH 1588 7-Cl-Q —CH═CH— H 9-CH₂OH —OCH₂COOH 1589 7-Cl-Q —CH═CH— H 9-CH₂OH —SCH₂CH₂COOH 1590 7-Cl-Q —CH═CH— H 8-CH₂OH —OCH₂COOH 1591 7-Cl-Q —CH═CH— H 8-CH₂OH —SCH₂CH₂COOH 1592 7-Cl-Q —CH═CH— H 7-CH₂OH —OCH₂COOH 1593 7-Cl-Q —CH═CH— H 7-CH₂OH —SCH₂CH₂COOH 1594 7-Cl-Q —CH═CH— H 9- —OCH₂COOH C(CH₃)₂OH 1595 7-Cl-Q —CH═CH— H 9- —SCH₂CH₂COOH C(CH₃)₂OH 1596 7-Cl-Q —CH═CH— H 8- —OCH₂COOH C(CH₃)₂OH 1597 7-Cl-Q —CH═CH— H 8- —SCH₂CH₂COOH C(CH₃)₂OH 1598 7-Cl-Q —CH═CH— H 7- —OCH₂COOH C(CH₃)₂OH 1599 7-Cl-Q —CH═CH— H 7- —SCH₂CH₂COOH C(CH₃)₂OH 1600 7-Cl-Q —CH═CH— H 9-OCH₃ —OCH₂COOH 1601 7-Cl-Q —CH═CH— H 9-OCH₃ —SCH₂CH₂COOH 1602 7-Cl-Q —CH═CH— H 8-OCH₃ —OCH₂COOH 1603 7-Cl-Q —CH═CH— H 8-OCH₃ —SCH₂CH₂COOH 1604 7-Cl-Q —CH═CH— H 7-OCH₃ —OCH₂COOH 1605 7-Cl-Q —CH═CH— H 7-OCH₃ —SCH₂CH₂COOH 1606 7-Cl-Q —CH═CH— H 9-OCHF₂ —OCH₂COOH 1607 7-Cl-Q —CH═CH— H 9-OCHF₂ —SCH₂CH₂COOH 1608 7-Cl-Q —CH═CH— H 8-OCHF₂ —OCH₂COOH 1609 7-Cl-Q —CH═CH— H 8-OCHF₂ —SCH₂CH₂COOH 1610 7-Cl-Q —CH═CH— H 7-OCHF₂ —OCH₂COOH 1611 7-Cl-Q —CH═CH— H 7-OCHF₂ —SCH₂CH₂COOH 1612 7-Cl-Q —CH═CH— H 9-OCF₃ —OCH₂COOH 1613 7-Cl-Q —CH═CH— H 9-OCF₃ —SCH₂CH₂COOH 1614 7-Cl-Q —CH═CH— H 8-OCF₃ —OCH₂COOH 1615 7-Cl-Q —CH═CH— H 8-OCF₃ —SCH₂CH₂COOH 1616 7-Cl-Q —CH═CH— H 7-OCF₃ —OCH₂COOH 1617 7-Cl-Q —CH═CH— H 7-CCF₃ —SCH₂CH₂COOH 1618 7-Cl-Q —CH═CH— H 9-SOCH₃ —OCH₂COOH 1619 7-Cl-Q —CH═CH— H 9-SOCH₃ —SCH₂CH₂COOH 1620 7-Cl-Q —CH═CH— H 8-SOCH₃ —OCH₂COOH 1621 7-Cl-Q —CH═CH— H 8-SOCH₃ —SCH₂CH₂COOH 1622 7-Cl-Q —CH═CH— H 7-SOCH₃ —OCH₂COOH 1623 7-Cl-Q —CH═CH— H 7-SOCH₃ —SCH₂CH₂COOH 1624 7-Cl-Q —CH═CH— H 9-SO₂CH₃ —OCH₂COOH 1625 7-Cl-Q —CH═CH— H 9-SO₂CH₃ —SCH₂CH₂COOH 1626 7-Cl-Q —CH═CH— H 8-SO₂CH₃ —OCH₂COOH 1627 7-Cl-Q —CH═CH— H 8-SO₂CH₃ —SCH₂CH₂COOH 1628 7-Cl-Q —CH═CH— H 7-SO₂CH₃ —OCH₂COOH 1629 7-Cl-Q —CH═CH— H 7-SO₂CH₃ —SCH₂CH₂COOH 1630 7-Cl-Q —CH═CH— H 9-CH═CH₂ —SCH₂CH₂COOH 1631 7-Cl-Q —CH═CH— H 8-CH═CH₂ —SCH₂CH₂COOH 1632 7-Cl-Q —CH═CH— H 7-CH═CH₂ —SCH₂CH₂COOH 1633 7-Cl-Q —CH═CH— H 9-NO₂ —OCH₂COOH 1634 7-Cl-Q —CH═CH— H 9-NO₂ —SCH₂CH₂COOH 1635 7-Cl-Q —CH═CH— H 8-NO₂ —OCH₂COOH 1636 7-Cl-Q —CH═CH— H 8-NO₂ —SCH₂CH₂COOH 1637 7-Cl-Q —CH═CH— H 7-NO₂ —OCH₂COOH 1638 7-Cl-Q —CH═CH— H 7-NO₂ —SCH₂CH₂COOH 1639 7-Cl-Q —CH═CH— 1-F H —SCH₂CH₂COOH 1640 7-Cl-Q —CH═CH— 2-F H —SCH₂CH₂COOH 1641 7-Cl-Q —CH═CH— 1-Cl H —SCH₂CH₂COOH 1642 7-Cl-Q —CH═CH— 2-Cl H —SCH₂CH₂COOH 1643 7-Cl-Q —CH═CH— 1-CH₃ H —SCH₂CH₂COOH 1644 7-Cl-Q —CH═CH— 2-CH₃ H —SCH₂CH₂COOH 1645 7-Cl-Q —CH═CH— 1-OCH₃ H —SCH₂CH₂COOH 1646 7-Cl-Q —CH═CH— 2-OCH₃ H —SCH₂CH₂COOH 1647 7-Cl-Q —CH═CH— 1-NO₂ H —SCH₂CH₂COOH 1648 7-Cl-Q —CH═CH— 2-NO₂ H —SCH₂CH₂COOH 1649 7-Cl-Q —CH═CH— 1-CN H —SCH₂CH₂COOH 1650 7-Cl-Q —CH═CH— 2-CN H —SCH₂CH₂COOH 1651 7-Cl-Q —CH₂O— H H —OCH₂COOH 1652 7-Cl-Q —CH₂O— H H —OCH(CH₃)COOH 1653 7-Cl-Q —CH₂O— H H —OCH₂CH₂COOH 1654 7-Cl-Q —CH₂O— H H —OCH₂CH(CH₃)COOH 1655 7-Cl-Q —CH₂O— H H —OCH₂C(CH₂CH₂)CH₂COOH 1656 7-Cl-Q —CH₂O— H H —SCH₂COOH 1657 7-Cl-Q —CH₂O— H H —SCH(CH3)COOH 1658 7-Cl-Q —CH₂O— H H —SCH₂CH₂COOH 1659 7-Cl-Q —CH₂O— H H —SCH₂CH(CH₃)COOH 1660 7-Cl-Q —CH₂O— H H —SCH₂C(CH₃)₂COOH 1661 7-Cl-Q —CH₂O— H H —SCH₂CH(CH₂CH₃)COOH 1662 7-Cl-Q —CH₂O— H H —SCH(CH₃)CH₂COOH 1663 7-Cl-Q —CH₂O— H H —SC(CH₃)₂CH₂COOH 1664 7-Cl-Q —CH₂O— H H —SCH₂CH₂CH₂COOH 1665 7-Cl-Q —CH₂O— H H —SCH₂CH(CH₃)CH₂COOH 1666 7-Cl-Q —CH₂O— H H —SCH₂C(CH₃)₂CH₂COOH 1667 7-Cl-Q —CH₂O— H H —SCH₂C(CH₂CH₂)CH₂COOH 1668 7-Cl-Q —CH₂O— H H —SCH₂CF₂COOH 1669 7-Cl-Q —CH₂O— H H —SCH₂CF₂CH₂COOH 1670 7-Cl-Q —CH₂O— H H —SCH₂-Tet 1671 7-Cl-Q —CH₂O— H H —SCH₂CH₂-Tet 1672 7-Cl-Q —CH₂O— H H —SCH₂NHSO₂CF₃ 1673 7-Cl-Q —CH₂O— H H —SCH₂CONHSO₂CH₃ 1674 7-Cl-Q —CH₂O— H H —SCH₂CONHSO₂CF₃ 1675 7-Cl-Q —CH₂O— H H —SCH₂CONHSO₂Ph 1676 7-Cl-Q —CH₂O— H H —SCH₂CONHSO₂(2-CH₃—Ph) 1677 7-Cl-Q —CH₂O— H H —SCH₂CH₂NHSO₂CF₃ 1678 7-Cl-Q —CH₂O— H H —SCH₂CH₂CONHSO₂CH₃ 1679 7-Cl-Q —CH₂O— H H —SCH₂CH₂CONHSO₂CF₃ 1680 7-Cl-Q —CH₂O— H H —SCH₂CH₂CONHSO₂Ph 1681 7-Cl-Q —CH₂O— H H —SCH₂CH₂CONHSO₂(2-CH₃—Ph) 1682 7-Cl-Q —CH₂O— H H —CH₂COOH 1683 7-Cl-Q —CH₂O— H H —CH₂CH₂COOH 1684 7-Cl-Q —CH₂O— H H —CH₂CH₂CH₂COOH 1685 7-Cl-Q —CH₂O— H 9-F —OCH₂COOH 1686 7-Cl-Q —CH₂O— H 9-F —OCH(CH₃)COOH 1687 7-Cl-Q —CH₂O— H 9-F —OCH₂CH₂COOH 1688 7-Cl-Q —CH₂O— H 9-F —OCH₂CH(CH3)COOH 1689 7-Cl-Q —CH₂O— H 9-F —OCH₂C(CH₂CH₂)CH₂COOH 1690 7-Cl-Q —CH₂O— H 9-F —SCH₂COOH 1691 7-Cl-Q —CH₂O— H 9-F —SCH(CH₃)COOH 1692 7-Cl-Q —CH₂O— H 9-F —SCH₂CH₂COOH 1693 7-Cl-Q —CH₂O— H 9-F —SCH₂CH(CH₃)COOH 1694 7-Cl-Q —CH₂O— H 9-F —SCH₂C(CH₂CH₂)CH₂COOH 1695 7-Cl-Q —CH₂O— H 8-F —OCH₂COOH 1696 7-Cl-Q —CH₂O— H 8-F —OCH₂CH₂COOH 1697 7-Cl-Q —CH₂O— H 8-F —SCH₂COOH 1698 7-Cl-Q —CH₂O— H 8-F —SCH₂CH₂COOH 1699 7-Cl-Q —CH₂O— H 8-F —SCH₂CH(CH₃)COOH 1700 7-Cl-Q —CH₂O— H 8-F —SCH₂C(CH₂CH₂)CH₂COOH 1701 7-Cl-Q —CH₂O— H 7-F —OCH₂COOH 1702 7-Cl-Q —CH₂O— H 7-F —OCH₂CH₂COOH 1703 7-Cl-Q —CH₂O— H 7-F —SCH₂COOH 1704 7-Cl-Q —CH₂O— H 7-F —SCH₂CH₂COOH 1705 7-Cl-Q —CH₂O— H 7-F —SCH₂CH(CH₃)COOH 1706 7-Cl-Q —CH₂O— H 6-F —OCH₂COOH 1707 7-Cl-Q —CH₂O— H 6-F —OCH(CH₃)COOH 1708 7-Cl-Q —CH₂O— H 6-F —OCH₂CH₂COOH 1709 7-Cl-Q —CH₂O— H 6-F —OCH₂CH(CH3)COOH 1710 7-Cl-Q —CH₂O— H 6-F —OCH₂C(CH₂CH₂)CH₂COOH 1711 7-Cl-Q —CH₂O— H 6-F —SCH₂COOH 1712 7-Cl-Q —CH₂O— H 6-F —SCH(CH₃)COOH 1713 7-Cl-Q —CH₂O— H 6-F —SCH₂CH₂COOH 1714 7-Cl-Q —CH₂O— H 6-F —SCH₂CH(CH₃)COOH 1715 7-Cl-Q —CH₂O— H 6-F —SCH₂C(CH₂CH₂)CH₂COOH 1716 7-Cl-Q —CH₂O— H 9-Cl —OCH₂COOH 1717 7-Cl-Q —CH₂O— H 9-Cl —OCH(CH₃)COOH 1718 7-Cl-Q —CH₂O— H 9-Cl —OCH₂CH₂COOH 1719 7-Cl-Q —CH₂O— H 9-Cl —OCH₂CH(CH3)COOH 1720 7-Cl-Q —CH₂O— H 9-Cl —OCH₂C(CH₂CH₂)CH₂COOH 1721 7-Cl-Q —CH₂O— H 9-Cl —SCH₂COOH 1722 7-Cl-Q —CH₂O— H 9-Cl —SCH(CH₃)COOH 1723 7-Cl-Q —CH₂O— H 9-Cl —SCH₂CH₂COOH 1724 7-Cl-Q —CH₂O— H 9-Cl —SCH₂CH(CH₃)COOH 1725 7-Cl-Q —CH₂O— H 9-Cl —SCH₂C(CH₂CH₂)CH₂COOH 1726 7-Cl-Q —CH₂O— H 8-Cl —SCH₂C(CH₂CH₂)CH₂COOH 1727 7-Cl-Q —CH₂O— H 8-Cl —OCH₂COOH 1728 7-Cl-Q —CH₂O— H 8-Cl —OCH₂CH₂COOH 1729 7-Cl-Q —CH₂O— H 8-Cl —SCH₂COOH 1730 7-Cl-Q —CH₂O— H 8-Cl —SCH₂CH₂COOH 1731 7-Cl-Q —CH₂O— H 8-Cl —SCH₂CH(CH₃)COOH 1732 7-Cl-Q —CH₂O— H 7-Cl —OCH₂COOH 1733 7-Cl-Q —CH₂O— H 7-Cl —OCH₂CH₂COOH 1734 7-Cl-Q —CH₂O— H 7-Cl —SCH₂COOH 1735 7-Cl-Q —CH₂O— H 7-Cl —SCH₂CH₂COOH 1736 7-Cl-Q —CH₂O— H 7-Cl —SCH₂CH(CH₃)COOH 1737 7-Cl-Q —CH₂O— H 9-CN —OCH₂COOH 1738 7-Cl-Q —CH₂O— H 9-CN —OCH(CH₃)COOH 1739 7-Cl-Q —CH₂O— H 9-CN —OCH₂CH₂COOH 1740 7-Cl-Q —CH₂O— H 9-CN —OCH₂CH(CH3)COOH 1741 7-Cl-Q —CH₂O— H 9-CN —OCH₂C(CH₂CH₂)CH₂COOH 1742 7-Cl-Q —CH₂O— H 9-CN —SCH₂COOH 1743 7-Cl-Q —CH₂O— H 9-CN —SCH(CH₃)COOH 1744 7-Cl-Q —CH₂O— H 9-CN —SCH₂CH₂COOH 1745 7-Cl-Q —CH₂O— H 9-CN —SCH₂CH(CH₃)COOH 1746 7-Cl-Q —CH₂O— H 9-CN —SCH₂C(CH₂CH₂)CH₂COOH 1747 7-Cl-Q —CH₂O— H 8-CN —OCH₂COOH 1748 7-Cl-Q —CH₂O— H 8-CN —OCH₂CH₂COOH 1749 7-Cl-Q —CH₂O— H 8-CN —SCH₂COOH 1750 7-Cl-Q —CH₂O— H 8-CN —SCH₂CH₂COOH 1751 7-Cl-Q —CH₂O— H 8-CN —SCH₂CH(CH₃)COOH 1752 7-Cl-Q —CH₂O— H 8-CN —SCH₂C(CH₂CH₂)CH₂COOH 1753 7-Cl-Q —CH₂O— H 7-CN —OCH₂COOH 1754 7-Cl-Q —CH₂O— H 7-CN —OCH₂CH₂COOH 1755 7-Cl-Q —CH₂O— H 7-CN —SCH₂COOH 1756 7-Cl-Q —CH₂O— H 7-CN —SCH₂CH₂COOH 1757 7-Cl-Q —CH₂O— H 7-CN —SCH₂CH(CH₃)COOH 1758 7-Cl-Q —CH₂O— H 9-CH₃ —OCH₂COOH 1759 7-Cl-Q —CH₂O— H 9-CH₃ —OCH₂CH₂COOH 1760 7-Cl-Q —CH₂O— H 9-CH₃ —SCH₂COOH 1761 7-Cl-Q —CH₂O— H 9-CH₃ —SCH₂CH₂COOH 1762 7-Cl-Q —CH₂O— H 9-CH₃ —SCH₂CH(CH₃)COOH 1763 7-Cl-Q —CH₂O— H 9-CH₃ —SCH₂CH(CH₂CH₃)COOH 1764 7-Cl-Q —CH₂O— H 9-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 1765 7-Cl-Q —CH₂O— H 8-CH₃ —OCH₂COOH 1766 7-Cl-Q —CH₂O— H 8-CH₃ —OCH₂CH₂COOH 1767 7-Cl-Q —CH₂O— H 8-CH₃ —SCH₂COOH 1768 7-Cl-Q —CH₂O— H 8-CH₃ —SCH₂CH₂COOH 1769 7-Cl-Q —CH₂O— H 8-CH₃ —SCH₂CH(CH₃)COOH 1770 7-Cl-Q —CH₂O— H 8-CH₃ —SCH₂C(CH₂CH₂)CH₂COOH 1771 7-Cl-Q —CH₂O— H 7-CH₃ —OCH₂COOH 1772 7-Cl-Q —CH₂O— H 7-CH₃ —OCH₂CH₂COOH 1773 7-Cl-Q —CH₂O— H 7-CH₃ —SCH₂COOH 1774 7-Cl-Q —CH₂O— H 7-CH₃ —SCH₂CH₂COOH 1775 7-Cl-Q —CH₂O— H 7-CH₃ —SCH₂CH(CH₃)COOH 1776 7-Cl-Q —CH₂O— H 9-CF₃ —OCH₂COOH 1777 7-Cl-Q —CH₂O— H 9-CF₃ —OCH(CH₃)COOH 1778 7-Cl-Q —CH₂O— H 9-CF₃ —OCH₂CH₂COOH 1779 7-Cl-Q —CH₂O— H 9-CF₃ —OCH₂CH(CH3)COOH 1780 7-Cl-Q —CH₂O— H 9-CF₃ —OCH₂C(CH₂CH₂)CH₂COOH 1781 7-Cl-Q —CH₂O— H 9-CF₃ —SCH₂COOH 1782 7-Cl-Q —CH₂O— H 9-CF₃ —SCH(CH₃)COOH 1783 7-Cl-Q —CH₂O— H 9-CF₃ —SCH₂CH₂COOH 1784 7-Cl-Q —CH₂O— H 9-CF₃ —SCH₂CH(CH₃)COOH 1785 7-Cl-Q —CH₂O— H 9-CF₃ —SCH₃C(CH₂CH₂)CH₂COOH 1786 7-Cl-Q —CH₂O— H 8-CF₃ —OCH₂COOH 1787 7-Cl-Q —CH₂O— H 8-CF₃ —OCH₂CH₂COOH 1788 7-Cl-Q —CH₂O— H 8-CF₃ —SCH₂COOH 1789 7-Cl-Q —CH₂O— H 8-CF₃ —SCH₂CH₂COOH 1790 7-Cl-Q —CH₂O— H 8-CF₃ —SCH₂CH(CH₃)COOH 1791 7-Cl-Q —CH₂O— H 8-CF₃ —SCH₃C(CH₂CH₂)CH₂COOH 1792 7-Cl-Q —CH₂O— H 7-CF₃ —OCH₂COOH 1793 7-Cl-Q —CH₂O— H 7-CF₃ —OCH₂CH₂COOH 1794 7-Cl-Q —CH₂O— H 7-CF₃ —SCH₂COOH 1795 7-Cl-Q —CH₂O— H 7-CF₃ —SCH₂CH₂COOH 1796 7-Cl-Q —CH₂O— H 7-CF₃ —SCH₂CH(CH₃)COOH 1797 7-Cl-Q —CH₂O— H 9-C≡CH —OCH₂COOH 1798 7-Cl-Q —CH₂O— H 9-C≡CH —OCH(CH₃)COOH 1799 7-Cl-Q —CH₂O— H 9-C≡CH —OCH₂CH₂COOH 1800 7-Cl-Q —CH₂O— H 9-C≡CH —OCH₂CH(CH3)COOH 1801 7-Cl-Q —CH₂O— H 9-C≡CH —OCH₂C(CH₂CH₂)CH₂COOH 1802 7-Cl-Q —CH₂O— H 9-C≡CH —SCH₂COOH 1803 7-Cl-Q —CH₂O— H 9-C≡CH —SCH(CH₃)COOH 1804 7-Cl-Q —CH₂O— H 9-C≡CH —SCH₂CH₂COOH 1805 7-Cl-Q —CH₂O— H 9-C≡CH —SCH₂CH(CH₃)COOH 1806 7-Cl-Q —CH₂O— H 9-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 1807 7-Cl-Q —CH₂O— H 8-C≡CH —OCH₂COOH 1808 7-Cl-Q —CH₂O— H 8-C≡CH —OCH₂CH₂COOH 1809 7-Cl-Q —CH₂O— H 8-C≡CH —SCH₂COOH 1810 7-Cl-Q —CH₂O— H 8-C≡CH —SCH₂CH₂COOH 1811 7-Cl-Q —CH₂O— H 8-C≡CH —SCH₂CH(CH₃)COOH 1812 7-Cl-Q —CH₂O— H 8-C≡CH —SCH₂C(CH₂CH₂)CH₂COOH 1813 7-Cl-Q —CH₂O— H 7-C≡CH —OCH₂COOH 1814 7-Cl-Q —CH₂O— H 7-C≡CH —OCH₂CH₂COOH 1815 7-Cl-Q —CH₂O— H 7-C≡CH —SCH₂COOH 1816 7-Cl-Q —CH₂O— H 7-C≡CH —SCH₂CH₂COOH 1817 7-Cl-Q —CH₂O— H 7-C≡CH —SCH₂CH(CH₃)COOH 1818 7-Cl-Q —CH₂O— H 9-CH₂OH —OCH₂COOH 1819 7-Cl-Q —CH₂O— H 9-CH₂OH —SCH₂CH₂COOH 1820 7-Cl-Q —CH₂O— H 8-CH₂OH —OCH₂COOH 1821 7-Cl-Q —CH₂O— H 8-CH₂OH —SCH₂CH₂COOH 1822 7-Cl-Q —CH₂O— H 7-CH₂OH —OCH₂COOH 1823 7-Cl-Q —CH₂O— H 7-CH₂OH —SCH₂CH₂COOH 1824 7-Cl-Q —CH₂O— H 9- —OCH₂COOH C(CH₃)₂OH 1825 7-Cl-Q —CH₂O— H 9- —SCH₂CH₂COOH C(CH₃)₂OH 1826 7-Cl-Q —CH₂O— H 8- —OCH₂COOH C(CH₃)₂OH 1827 7-Cl-Q —CH₂O— H 8- —SCH₂CH₂COOH C(CH₃)₂OH 1828 7-Cl-Q —CH₂O— H 7- —OCH₂COOH C(CH₃)₂OH 1829 7-Cl-Q —CH₂O— H 7- —SCH₂CH₂COOH C(CH₃)₂OH 1830 7-Cl-Q —CH₂O— H 9-OCH₃ —OCH₂COOH 1831 7-Cl-Q —CH₂O— H 9-OCH₃ —SCH₂CH₂COOH 1832 7-Cl-Q —CH₂O— H 8-OCH₃ —OCH₂COOH 1833 7-Cl-Q —CH₂O— H 8-OCH₃ —SCH₂CH₂COOH 1834 7-Cl-Q —CH₂O— H 7-OCH₃ —OCH₂COOH 1835 7-Cl-Q —CH₂O— H 7-OCH₃ —SCH₂CH₂COOH 1836 7-Cl-Q —CH₂O— H 9-OCHF₂ —OCH₂COOH 1837 7-Cl-Q —CH₂O— H 9-COHF₂ —SCH₂CH₂COOH 1838 7-Cl-Q —CH₂O— H 8-OCHF₂ —OCH₂COOH 1839 7-Cl-Q —CH₂O— H 8-OCHF₂ —SCH₂CH₂COOH 1840 7-Cl-Q —CH₂O— H 7-OCHF₂ —OCH₂COOH 1841 7-Cl-Q —CH₂O— H 7-OCHF₂ —SCH₂CH₂COOH 1842 7-Cl-Q —CH₂O— H 9-OCF₃ —OCH₂COOH 1843 7-Cl-Q —CH₂O— H 9-OCF₃ —SCH₂CH₂COOH 1844 7-Cl-Q —CH₂O— H 8-OCF₃ —OCH₂COOH 1845 7-Cl-Q —CH₂O— H 8-OCF₃ —SCH₂CH₂COOH 1846 7-Cl-Q —CH₂O— H 7-OCF₃ —OCH₂COOH 1847 7-Cl-Q —CH₂O— H 7-OCF₃ —SCH₂CH₂COOH 1848 7-Cl-Q —CH₂O— H 9-SOCH₃ —OCH₂COOH 1849 7-Cl-Q —CH₂O— H 9-SOCH₃ —SCH₂CH₂COOH 1850 7-Cl-Q —CH₂O— H 8-SOCH₃ —OCH₂COOH 1851 7-Cl-Q —CH₂O— H 8-SOCH₃ —SCH₂CH₂COOH 1852 7-Cl-Q —CH₂O— H 7-SOCH₃ —OCH₂COOH 1853 7-Cl-Q —CH₂O— H 7-SOCH₃ —SCH₂CH₂COOH 1854 7-Cl-Q —CH₂O— H 9-SO₂CH₃ —OCH₂COOH 1855 7-Cl-Q —CH₂O— H 9-SO₂CH₃ —SCH₂CH₂COOH 1856 7-Cl-Q —CH₂O— H 8-SOCH₃ —OCH₂COOH 1857 7-Cl-Q —CH₂O— H 8-SO₂CH₃ —SCH₂CH₂COOH 1858 7-Cl-Q —CH₂O— H 7-SO₂CH₃ —OCH₂COOH 1859 7-Cl-Q —CH₂O— H 7-SO₂CH₃ —SCH₂CH₂COOH 1860 7-Cl-Q —CH₂O— H 9-CH═CH₂ —SCH₂CH₂COOH 1861 7-Cl-Q —CH₂O— H 8-CH═CH₂ —SCH₂CH₂COOH 1862 7-Cl-Q —CH₂O— H 7-CH═CH₂ —SCH₂CH₂COOH 1863 7-Cl-Q —CH₂O— H 9-NO₂ —OCH₂COOH 1864 7-Cl-Q —CH₂O— H 9-NO₂ —SCH₂CH₂COOH 1865 7-Cl-Q —CH₂O— H 8-NO₂ —OCH₂COOH 1866 7-Cl-Q —CH₂O— H 8-NO₂ —SCH₂CH₂COOH 1867 7-Cl-Q —CH₂O— H 7-NO₂ —OCH₂COOH 1868 7-Cl-Q —CH₂O— H 7-NO₂ —SCH₂CH₂COOH 1869 7-Cl-Q —CH₂O— 1-F H —SCH₂CH₂COOH 1870 7-Cl-Q —CH₂O— 2-F H —SCH₂CH₂COOH 1871 7-Cl-Q —CH₂O— 1-Cl H —SCH₂CH₂COOH 1872 7-Cl-Q —CH₂O— 2-Cl H —SCH₂CH₂COOH 1873 7-Cl-Q —CH₂O— 1-CH₃ H —SCH₂CH₂COOH 1874 7-Cl-Q —CH₂O— 2-CH₃ H —SCH₂CH₂COOH 1875 7-Cl-Q —CH₂O— 1-OCH₃ H —SCH₂CH₂COOH 1876 7-Cl-Q —CH₂O— 2-OCH₃ H —SCH₂CH₂COOH 1877 7-Cl-Q —CH₂O— 1-NO₂ H —SCH₂CH₂COOH 1878 7-Cl-Q —CH₂O— 2-NO₂ H —SCH₂CH₂COOH 1879 7-Cl-Q —CH₂O— 1-CN H —SCH₂CH₂COOH 1880 7-Cl-Q —CH₂O— 2-CN H —SCH₂CH₂COOH 1881 TQ —CH═CH— H H —OCH₂COOH 1882 TQ —CH═CH— H H —OCH₂CH₂COOH 1883 TQ —CH═CH— H H —OCH₂CH(CH₃)COOH 1884 TQ —CH═CH— H H —SCH₂COOH 1885 TQ —CH═CH— H H —SCH₂CH₂COOH 1886 TQ —CH═CH— H H —SCH₂CH(CH₃)COOH 1887 TQ —CH═CH— H H —SCH₂C(CH₃)₂COOH 1888 TQ —CH═CH— H H —SCH₂CH(CH₂CH₃)COOH 1889 TQ —CH═CH— H H —SCH(CH₃)CH₂COOH 1890 TQ —CH═CH— H H —SC(CH₃)₂CH₂COOH 1891 TQ —CH═CH— H H —SCH₂CH₂CH₂COOH 1892 TQ —CH═CH— H H —SCH₂CH(CH₃)CH₂COOH 1893 TQ —CH═CH— H H —SCH₂C(CH₃)₂CH₂COOH 1894 TQ —CH═CH— H H —SCH₂C(CH₂CH₂)CH₂COOH 1895 TQ —CH═CH— H H —SCH₂CF₂COOH 1896 TQ —CH═CH— H H —SCH₂CF₂CH₂COOH 1897 TQ —CH═CH— H H —SCH₂CONHSO₂CH₃ 1898 TQ —CH═CH— H H —SCH₂CONHSO₂CF₃ 1899 TQ —CH═CH— H H —SCH₂CH₂NHSO₂CF₃ 1900 TQ —CH═CH— H H —SCH₂CH₂CONHSO₂CH₃ 1901 TQ —CH═CH— H H —SCH₂CH₂CONHSO₂CF₃ 1902 TQ —CH═CH— H H —CH₂CH₂COOH 1903 TQ —CH═CH— H H —CH₂CH₂CH₂COOH 1904 TQ —CH═CH— H 9-F —OCH₂COOH 1905 TQ —CH═CH— H 9-F —OCH₂CH₂COOH 1906 TQ —CH═CH— H 9-F —SCH₂COOH 1907 TQ —CH═CH— H 9-F —SCH₂CH₂COOH 1908 TQ —CH═CH— H 8-F —OCH₂COOH 1909 TQ —CH═CH— H 8-F —OCH₂CH₂COOH 1910 TQ —CH═CH— H 8-F —SCH₂COOH 1911 TQ —CH═CH— H 8-F —SCH₂CH₂COOH 1912 TQ —CH═CH— H 9-CN —OCH₂COOH 1913 TQ —CH═CH— H 9-CN —OCH₂CH₂COOH 1914 TQ —CH═CH— H 9-CN —SCH₂COOH 1915 TQ —CH═CH— H 9-CN —SCH₂CH₂COOH 1916 TQ —CH═CH— H 8-CN —OCH₂COOH 1917 TQ —CH═CH— H 8-CN —OCH₂CH₂COOH 1918 TQ —CH═CH— H 8-CN —SCH₂COOH 1919 TQ —CH═CH— H 8-CN —SCH₂CH₂COOH 1920 TQ —CH═CH— H 9-CF₃ —OCH₂COOH 1921 TQ —CH═CH— H 9-CF₃ —SCH₂CH₂COOH 1922 TQ —CH═CH— H 8-CF₃ —OCH₂COOH 1923 TQ —CH═CH— H 8-CF₃ —SCH₂CH₂COOH 1924 TQ —CH═CH— H 9-C≡CH —OCH₂COOH 1925 TQ —CH═CH— H 9-C≡CH —SCH₂CH₂COOH 1926 TQ —CH═CH— H 8-C≡CH —SCH₂CH₂COOH 1927 TQ —CH₂O— H H —OCH₂COOH 1928 TQ —CH₂O— H H —OCH₂CH₂COOH 1929 TQ —CH₂O— H H —OCH₂CH(CH₃)COOH 1930 TQ —CH₂O— H H —SCH₂COOH 1931 TQ —CH₂O— H H —SCH₂CH₂COOH 1932 TQ —CH₂O— H H —SCH₂CH(CH₃)COOH 1933 TQ —CH₂O— H H —SCH₂C(CH₃)₂COOH 1934 TQ —CH₂O— H H —SCH₂CH(CH₂CH₃)COOH 1935 TQ —CH₂O— H H —SCH(CH₃)CH₂COOH 1936 TQ —CH₂O— H H —SC(CH₃)₂CH₂COOH 1937 TQ —CH₂O— H H —SCH₂CH₂CH₂COOH 1938 TQ —CH₂O— H H —SCH₂CH(CH₃)CH₂COOH 1939 TQ —CH₂O— H H —SCH₂C(CH₃)₂CH₂COOH 1940 TQ —CH₂O— H H —SCH₂C(CH₂CH₂)CH₂COOH 1941 TQ —CH₂O— H H —SCH₂CF₂COOH 1942 TQ —CH₂O— H H —SCH₂CF₂CH₂COOH 1943 TQ —CH₂O— H H —SCH₂CONHSO₂CH₃ 1944 TQ —CH₂O— H H —SCH₂CONHSO₂CF₃ 1945 TQ —CH₂O— H H —SCH₂CH₂NHSO₂CF₃ 1946 TQ —CH₂O— H H —SCH₂CH₂CONHSO₂CH₃ 1947 TQ —CH₂O— H H —SCH₂CH₂CONHSO₂CF₃ 1948 TQ —CH₂O— H H —CH₂CH₂COOH 1949 TQ —CH₂O— H H —CH₂CH₂CH₂COOH 1950 TQ —CH₂O— H 9-F —OCH₂COOH 1951 TQ —CH₂O— H 9-F —OCH₂CH₂COOH 1952 TQ —CH₂O— H 9-F —SCH₂COOH 1953 TQ —CH₂O— H 9-F —SCH₂CH₂COOH 1954 TQ —CH₂O— H 8-F —OCH₂COOH 1955 TQ —CH₂O— H 8-F —OCH₂CH₂COOH 1956 TQ —CH₂O— H 8-F —SCH₂COOH 1957 TQ —CH₂O— H 8-F —SCH₂CH₂COOH 1958 TQ —CH₂O— H 9-CN —OCH₂COOH 1959 TQ —CH₂O— H 9-CN —OCH₂CH₂COOH 1960 TQ —CH₂O— H 9-CN —SCH₂COOH 1961 TQ —CH₂O— H 9-CN —SCH₂CH₂COOH 1962 TQ —CH₂O— H 8-CN —OCH₂COOH 1963 TQ —CH₂O— H 8-CN —OCH₂CH₂COOH 1964 TQ —CH₂O— H 8-CN —SCH₂COOH 1965 TQ —CH₂O— H 8-CN —SCH₂CH₂COOH 1966 TQ —CH₂O— H 9-CF₃ —OCH₂COOH 1967 TQ —CH₂O— H 9-CF₃ —SCH₂CH₂COOH 1968 TQ —CH₂O— H 8-CF₃ —OCH₂COOH 1969 TQ —CH₂O— H 8-CF₃ —SCH₂CH₂COOH 1970 TQ —CH₂O— H 9-C≡CH —OCH₂COOH 1971 TQ —CH₂O— H 9-C≡CH —SCH₂CH₂COOH 1972 TQ —CH₂O— H 8-C≡CH —SCH₂CH₂COOH 1973 7-CF₃-Q —CH═CH— H H —OCH₂COOH 1974 7-CF₃-Q —CH═CH— H H —OCH₂CH₂COOH 1975 7-CF₃-Q —CH═CH— H H —SCH₂COOH 1976 7-CF₃-Q —CH═CH— H H —SCH₂CH₂COOH 1977 7-CF₃-Q —CH═CH— H H —SCH₂CH(CH₃)COOH 1978 7-CF₃-Q —CH═CH— H H —SCH₂C(CH₂CH₂)CH₂COOH 1979 7-CF₃-Q —CH₂O— H H —OCH₂COOH 1980 7-CF₃-Q —CH₂O— H H —OCH₂CH₂COOH 1981 7-CF₃-Q —CH₂O— H H —SCH₂COOH 1982 7-CF₃-Q —CH₂O— H H —SCH₂CH₂COOH 1983 7-CF₃-Q —CH₂O— H H —SCH₂CH(CH₃)COOH 1984 7-CF₃-Q —CH₂O— H H —SCH₂C(CH₂CH₂)CH₂COOH 1985 6-F,7-CF₃-Q —CH═CH— H H —OCH₂COOH 1986 6-F,7-CF₃-Q —CH═CH— H H —OCH₂CH₂COOH 1987 6-F,7-CF₃-Q —CH═CH— H H —SCH₂COOH 1988 6-F,7-CF₃-Q —CH═CH— H H —SCH₂CH₂COOH 1989 6-F,7-CF₃-Q —CH═CH— H H —SCH₂CH(CH₃)COOH 1990 6-F,7-CF₃-Q —CH═CH— H H —SCH₂C(CH₂CH₂)CH₂COOH 1991 6-F,7-CF₃-Q —CH₂O— H H —OCH₂COOH 1992 6-F,7-CF₃-Q —CH₂O— H H —OCH₂CH₂COOH 1993 6-F,7-CF₃-Q —CH₂O— H H —SCH₂COOH 1994 6-F,7-CF₃-Q —CH₂O— H H —SCH₂CH₂COOH 1995 6-F,7-CF₃-Q —CH₂O— H H —SCH₂CH(CH₃)COOH 1996 6-F,7-CF₃-Q —CH₂O— H H —SCH₂C(CH₂CH₂)CH₂COOH 1997 6,7-diCl-Q —CH═CH— H H —OCH₂COOH 1998 6,7-diCl-Q —CH═CH— H H —OCH₂CH₂COOH 1999 6,7-diCl-Q —CH═CH— H H —SCH₂COOH 2000 6,7-diCl-Q —CH═CH— H H —SCH₂CH₂COOH 2001 6,7-diCl-Q —CH═CH— H H —SCH₂CH(CH₃)COOH 2002 6,7-diCl-Q —CH═CH— H H —SCH₂C(CH₂CH₂)CH₂COOH 2003 6,7-diCl-Q —CH₂O— H H —OCH₂COOH 2004 6,7-diCl-Q —CH₂O— H H —OCH₂CH₂COOH 2005 6,7-diCl-Q —CH₂O— H H —SCH₂COOH 2006 6,7-diCl-Q —CH₂O— H H —SCH₂CH₂COOH 2007 6,7-diCl-Q —CH₂O— H H —SCH₂CH(CH₃)COOH 2008 6,7-diCl-Q —CH₂O— H H —SCH₂C(CH₂CH₂)CH₂COOH 2009 6-Cl,7-F-Q —CH═CH— H H —OCH₂COOH 2010 6-Cl,7-F-Q —CH═CH— H H —OCH₂CH₂COOH 2011 6-Cl,7-F-Q —CH═CH— H H —SCH₂COOH 2012 6-Cl,7-F-Q —CH═CH— H H —SCH₂CH₂COOH 2013 6-Cl,7-F-Q —CH═CH— H H —SCH₂CH(CH₃)COOH 2014 6-Cl,7-F-Q —CH═CH— H H —SCH₂C(CH₂CH₂)CH₂COOH 2015 6-Cl,7-F-Q —CH₂O— H H —OCH₂COOH 2016 6-Cl,7-F-Q —CH₂O— H H —OCH₂CH₂COOH 2017 6-Cl,7-F-Q —CH₂O— H H —SCH₂COOH 2018 6-Cl,7-F-Q —CH₂O— H H —SCH₂CH₂COOH 2019 6-Cl,7-F-Q —CH₂O— H H —SCH₂CH(CH₃)COOH 2020 6-Cl,7-F-Q —CH₂O— H H —SCH₂C(CH₂CH₂)CH₂COOH 2021 5,6,7-triF-Q —CH═CH— H H —OCH₂COOH 2022 5,6,7-triF-Q —CH═CH— H H —OCH₂CH₂COOH 2023 5,6,7-triF-Q —CH═CH— H H —SCH₂COOH 2024 5,6,7-triF-Q —CH═CH— H H —SCH₂CH₂COOH 2025 5,6,7-triF-Q —CH₂O— H H —OCH₂COOH 2026 5,6,7-triF-Q —CH₂O— H H —OCH₂CH₂COOH 2027 5,6,7-triF-Q —CH₂O— H H —SCH₂COOH 2028 5,6,7-triF-Q —CH₂O— H H —SCH₂CH₂COOH 2029 4-t-Bu-T —CH═CH— H H —OCH₂COOH 2030 4-t-Bu-T —CH═CH— H H —SCH₂COOH 2031 4-t-Bu-T —CH═CH— H H —SCH₂CH₂COOH 2032 4-t-Bu-T —CH₂O— H H —OCH₂COOH 2033 4-t-Bu-T —CH₂O— H H —SCH₂COOH 2034 4-t-Bu-T —CH₂O— H H —SCH₂CH₂COOH 2035 5-F-BT —CH═CH— H H —OCH₂COOH 2036 5-F-BT —CH═CH— H H —SCH₂COOH 2037 5-F-BT —CH═CH— H H —SCH₂CH₂COOH 2038 5-F-BT —CH₂O— H H —OCH₂COOH 2039 5-F-BT —CH₂O— H H —SCH₂COOH 2040 5-F-BT —CH₂O— H H —SCH₂CH₂COOH 2041 5,6-diF-BT —CH═CH— H H —OCH₂COOH 2042 5,6-diF-BT —CH═CH— H H —SCH₂COOH 2043 5,6-diF-BT —CH═CH— H H —SCH₂CH₂COOH 2044 5,6-diF-BT —CH₂O— H H —OCH₂COOH 2045 5,6-diF-BT —CH₂O— H H —SCH₂COOH 2046 5,6-diF-BT —CH₂O— H H —SCH₂CH₂COOH 2047 6-t-Bu-Py —CH═CH— H H —OCH₂COOH 2048 6-t-Bu-Py —CH═CH— H H —SCH₂COOH 2049 6-t-Bu-Py —CH═CH— H H —SCH₂CH₂COOH 2050 6-t-Bu-Py —CH₂O— H H —OCH₂COOH 2051 6-t-Bu-Py —CH₂O— H H —SCH₂COOH 2052 6-t-Bu-Py —CH₂O— H H —SCH₂CH₂COOH 2053 6,7-diF-Q —CH₂CH₂— H H —OCH₂COOH 2054 6,7-diF-Q —CH₂CH₂— H H —SCH₂COOH 2055 6,7-diF-Q —CH₂CH₂— H H —SCH₂CH₂COOH 2056 6,7-diF-Q —CH₂S— H H —OCH₂COOH 2057 6,7-diF-Q —CH₂S— H H —SCH₂COOH 2058 6,7-diF-Q —CH₂S— H H —SCH₂CH₂COOH 2059 6,7-diF-Q —OCH₂— H H —OCH₂COOH 2060 6,7-diF-Q —OCH₂— H H —SCH₂COOH 2061 6,7-diF-Q —OCH₂— H H —SCH₂CH₂COOH 2062 6,7-diF-Q —SCH₂— H H —OCH₂COOH 2063 6,7-diF-Q —SCH₂— H H —SCH₂COOH 2064 6,7-diF-Q —SCH₂— H H —SCH₂CH₂COOH 2065 7-Cl,6-F-Q —CH₂CH₂— H H —OCH₂COOH 2066 7-Cl,6-F-Q —CH₂CH₂— H H —SCH₂COOH 2067 7-Cl,6-F-Q —CH₂CH₂— H H —SCH₂CH₂COOH 2068 7-Cl,6-F-Q —CH₂S— H H —OCH₂COOH 2069 7-Cl,6-F-Q —CH₂S— H H —SCH₂COOH 2070 7-Cl,6-F-Q —CH₂S— H H —SCH₂CH₂COOH 2071 7-Cl,6-F-Q —OCH₂— H H —OCH₂COOH 2072 7-Cl,6-F-Q —OCH₂— H H —SCH₂COOH 2073 7-Cl,6-F-Q —OCH₂— H H —SCH₂CH₂COOH 2074 7-Cl,6-F-Q —SCH₂— H H —OCH₂COOH 2075 7-Cl,6-F-Q —SCH₂— H H —SCH₂COOH 2076 7-Cl,6-F-Q —SCH₂— H H —SCH₂CH₂COOH 2077 7-F-Q —CH₂CH₂— H H —OCH₂COOH 2078 7-F-Q —CH₂CH₂— H H —SCH₂COOH 2079 7-F-Q —CH₂CH₂— H H —SCH₂CH₂COOH 2080 7-F-Q —CH₂S— H H —OCH₂COOH 2081 7-F-Q —CH₂S— H H —SCH₂COOH 2082 7-F-Q —CH₂S— H H —SCH₂CH₂COOH 2083 7-F-Q —OCH₂— H H —OCH₂COOH 2084 7-F-Q —OCH₂— H H —SCH₂COOH 2085 7-F-Q —OCH₂— H H —SCH₂CH₂COOH 2086 7-F-Q —SCH₂— H H —OCH₂COOH 2087 7-F-Q —SCH₂— H H —SCH₂COOH 2088 7-F-Q —SCH₂— H H —SCH₂CH₂COOH 2089 7-Cl-Q —CH₂CH₂— H H —OCH₂COOH 2090 7-Cl-Q —CH₂CH₂— H H —SCH₂COOH 2091 7-Cl-Q —CH₂CH₂— H H —SCH₂CH₂COOH 2092 7-Cl-Q —CH₂S— H H —OCH₂COOH 2093 7-Cl-Q —CH₂S— H H —SCH₂COOH 2094 7-Cl-Q —CH₂S— H H —SCH₂CH₂COOH 2095 7-C1-Q —OCH₂— H H —OCH₂COOH 2096 7-Cl-Q —OCH₂— H H —SCH₂COOH 2097 7-Cl-Q —OCH₂— H H —SCH₂CH₂COOH 2098 7-Cl-Q —SCH₂— H H —OCH₂COOH 2099 7-Cl-Q —SCH₂— H H —SCH₂COOH 2100 7-Cl-Q —SCH₂— H H —SCH₂CH₂COOH

[0080] Incidentally, in the above-mentioned table, the respective abbreviations mean t-Bu: t-butyl group, BT: 2-benzothiazolyl group, Tet: 1H-tetrazol-5-yl group, Ph: a phenyl group, Py: 2-pyridyl group, Q: quinolin-2-yl group, T: 2-thiazolyl group, and TQ: 5,6,7,8-tetrahydroquinolin-2-yl group,

[0081] and the CH₂C(CH₂CH₂)CH₂ portion in the —OCH₂C(CH₂CH₂)—CH₂COOH or —SCH₂C(CH₂CH₂)CH₂COOH represents the formula (a) wherein o=1, p=1 and q=1, and the CH₂C(CH₂CH₂) portion in the —SCH₂C(CH₂CH₂)COOH represents the formula (a) wherein o=1, p=0 and q=1. Also, in the above-mentioned Table 1, the numeral(s) in the formula (I) represents a substituted position(s) of the substituent(s).

[0082] As the more preferred compounds, there may be mentioned compounds of Compounds No. 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 24, 25, 27, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 47, 49, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 76, 78, 79, 87, 89, 92, 94, 97, 99, 102, 103, 104, 105, 106, 107, 110, 112, 118, 121, 122, 123, 124, 128, 136, 138, 139, 140, 141, 142, 143, 144, 145, 146, 149, 157, 159, 160, 161, 162, 163, 164, 165, 166, 167, 170, 179, 184, 185, 190, 191, 196, 197, 202, 203, 220, 223, 224, 241, 243, 244, 245, 246, 247, 248, 249, 250, 251, 257, 264, 273, 274, 275, 277, 280, 281, 282, 283, 284, 285, 288, 296, 298, 299, 300, 301, 302, 303, 304, 305, 306, 308, 309, 310, 311, 312, 313, 314, 315, 319, 320, 327, 329, 331, 332, 333, 334, 335, 336, 337, 340, 348, 351, 366, 368, 371, 372, 373, 374, 375, 376, 378, 379, 387, 392, 393, 394, 396, 397, 400, 420, 421, 426, 427, 429, 432, 433, 435, 453, 454, 455, 456, 471, 472, 473, 474, 475, 476, 477, 478, 479, 481, 482, 483, 484, 485, 486, 487, 494, 495, 497, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 517, 519, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 546, 548, 549, 557, 558, 559, 562, 564, 567, 569, 572, 573, 574, 575, 576, 577, 580, 582, 588, 591, 592, 593, 594, 598, 606, 608, 609, 610, 611, 612, 613, 614, 615, 616, 619, 627, 629, 630, 631, 632, 633, 634, 635, 636, 637, 640, 649, 654, 655, 660, 661, 666, 667, 672, 673, 690, 693, 694, 711, 713, 714, 715, 716, 717, 718, 719, 720, 721, 727, 734, 743, 744, 745, 747, 750, 751, 752, 753, 754, 755, 758, 766, 768, 769, 770, 771, 772, 773, 774, 775, 776, 778, 779, 780, 781, 782, 783, 784, 785, 789, 790, 797, 799, 801, 802, 803, 804, 805, 806, 807, 810, 818, 821, 836, 838, 841, 842, 843, 844, 845, 846, 848, 849, 857, 862, 863, 864, 866, 867, 870, 890, 891, 896, 897, 899, 902, 903, 905, 923, 924, 925, 926, 941, 942, 943, 944, 945, 946, 947, 948, 949, 951, 952, 953, 954, 955, 956, 957, 964, 965, 967, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982, 983, 984, 987, 989, 995, 996, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006, 1007, 1008, 1009, 1010, 1011, 1012, 1013, 1014, 1016, 1018, 1019, 1027, 1029, 1032, 1034, 1037, 1039, 1042, 1043, 1044, 1045, 1046, 1047, 1050, 1052, 1058, 1061, 1062, 1063, 1064, 1068, 1076, 1078, 1079, 1080, 1081, 1082, 1083, 1084, 1085, 1086, 1089, 1097, 1099, 1100, 1101, 1102, 1103, 1104, 1105, 1106, 1107, 1110, 1119, 1124, 1125, 1130, 1131, 1136, 1137, 1142, 1143, 1160, 1163, 1164, 1181, 1183, 1184, 1185, 1186, 1187, 1188, 1189, 1190, 1191, 1197, 1204, 1213, 1214, 1215, 1217, 1220, 1221, 1222, 1223, 1224, 1225, 1228, 1236, 1238, 1239, 1240, 1241, 1242, 1243, 1244, 1245, 1246, 1248, 1249, 1250, 1251, 1252, 1253, 1254, 1255, 1259, 1260, 1267, 1269, 1271, 1272, 1273, 1274, 1275, 1276, 1277, 1280, 1288, 1291, 1306, 1308, 1311, 1312, 1313, 1314, 1315, 1316, 1318, 1319, 1327, 1332, 1333, 1334, 1336, 1337, 1340, 1360, 1361, 1366, 1367, 1369, 1372, 1373, 1375, 1393, 1394, 1395, 1396, 1411, 1412, 1413, 1414, 1415, 1416, 1417, 1418, 1419, 1421, 1422, 1423, 1424, 1425, 1426, 1427, 1434, 1435, 1437, 1443, 1444, 1445, 1446, 1447, 1448, 1449, 1450, 1451, 1452, 1453, 1454, 1457, 1459, 1465, 1466, 1467, 1468, 1469, 1470, 1471, 1472, 1473, 1474, 1475, 1476, 1477, 1478, 1479, 1480, 1481, 1482, 1483, 1484, 1486, 1488, 1489, 1497, 1499, 1502, 1504, 1507, 1509, 1512, 1513, 1514, 1515, 1516, 1517, 1520, 1522, 1528, 1531, 1532, 1533, 1534, 1538, 1546, 1548, 1549, 1550, 1551, 1552, 1553, 1554, 1555, 1556, 1559, 1567, 1569, 1570, 1571, 1572, 1573, 1574, 1575, 1576, 1577, 1580, 1589, 1594, 1595, 1600, 1601, 1606, 1607, 1612, 1613, 1630, 1633, 1634, 1651, 1653, 1654, 1655, 1656, 1657, 1658, 1659, 1660, 1661, 1667, 1674, 1683, 1684, 1685, 1687, 1690, 1691, 1692, 1693, 1694, 1695, 1698, 1706, 1708, 1709, 1710, 1711, 1712, 1713, 1714, 1715, 1716, 1718, 1719, 1720, 1721, 1722, 1723, 1724, 1725, 1729, 1730, 1737, 1739, 1741, 1742, 1743, 1744, 1745, 1746, 1747, 1750, 1758, 1761, 1776, 1778, 1781, 1782, 1783, 1784, 1785, 1786, 1788, 1789, 1797, 1802, 1803, 1804, 1806, 1807, 1810, 1830, 1831, 1836, 1837, 1839, 1842, 1843, 1845, 1863, 1864, 1865, 1866, 1884, 1885, 1886, 1888, 1894, 1903, 1907, 1911, 1915, 1921, 1925, 1931, 1932, 1934, 1940, 1949, 1953, 1961, 1967, 1971, 1976, 1978, 1980, 1982, 1984, 1988, 1990, 1994, 1995, 1996, 2000, 2001, 2002, 2004, 2006, 2007, 2008, 2012, 2013, 2014, 2018, 2019, 2020, 2024, 2028, 2031, 2034, 2037, 2040, 2043, 2046, 2049, 2052, 2055, 2058, 2061, 2064, 2067, 2070, 2073, 2076, 2079, 2082, 2085, 2088, 2091, 2094, 2097 or 2100,

[0083] more preferably compounds are Compounds No. 1, 2, 3, 4, 6, 7, 8, 9, 11, 14, 15, 17, 35, 37, 38, 40, 41, 42, 43, 47, 49, 55, 57, 60, 62, 63, 64, 65, 66, 67, 70, 72, 73, 74, 78, 79, 87, 89, 92, 94, 97, 102, 104, 105, 106, 110, 121, 122, 123, 136, 138, 141, 143, 144, 145, 149, 157, 159, 162, 163, 164, 165, 166, 170, 191, 197, 202, 203, 220, 224, 241, 243, 246, 247, 248, 249, 251, 257, 275, 280, 282, 283, 284, 288, 296, 298, 301, 303, 304, 305, 306, 308, 311, 312, 313, 314, 315, 320, 327, 332, 334, 335, 336, 340, 351, 366, 371, 372, 373, 374, 375, 376, 379, 387, 393, 394, 400, 420, 421, 426, 427, 432, 433, 453, 456, 471, 473, 474, 476, 477, 478, 479, 481, 484, 485, 487, 505, 507, 508, 510, 511, 512, 513, 517, 519, 525, 527, 530, 532, 533, 534, 535, 536, 537, 540, 542, 543, 544, 548, 549, 557, 558, 559, 562, 564, 567, 572, 574, 575, 576, 580, 591, 592, 593, 606, 608, 611, 613, 614, 615, 619, 627, 629, 632, 633, 634, 635, 636, 640, 661, 667, 672, 673, 690, 694, 711, 713, 716, 717, 718, 719, 721, 727, 745, 750, 752, 753, 754, 758, 766, 768, 771, 773, 774, 775, 776, 778, 781, 782, 783, 784, 785, 790, 797, 802, 804, 805, 806, 810, 821, 836, 841, 842, 843, 844, 845, 846, 849, 857, 863, 864, 870, 890, 891, 896, 897, 902, 903, 923, 926, 941, 943, 944, 946, 947, 948, 949, 951, 954, 955, 957, 975, 977, 978, 980, 981, 982, 983, 987, 989, 995, 997, 1000, 1002, 1003, 1004, 1005, 1006, 1007, 1010, 1012, 1013, 1014, 1018, 1019, 1027, 1029, 1032, 1034, 1037, 1042, 1044, 1045, 1046, 1050, 1061, 1062, 1063, 1076, 1078, 1081, 1083, 1084, 1085, 1089, 1097, 1099, 1102, 1103, 1104, 1105, 1106, 1110, 1131, 1137, 1142, 1143, 1160, 1164, 1181, 1183, 1186, 1187, 1188, 1189, 1191, 1197, 1215, 1220, 1222, 1223, 1224, 1225, 1228, 1236, 1238, 1241, 1243, 1244, 1245, 1246, 1248, 1251, 1252, 1253, 1254, 1255, 1260, 1267, 1272, 1274, 1275, 1276, 1280, 1291, 1306, 1311, 1312, 1313, 1314, 1315, 1316, 1319, 1327, 1333, 1334, 1340, 1360, 1361, 1366, 1367, 1372, 1373, 1393, 1396, 1411, 1413, 1414, 1416, 1417, 1418, 1419, 1421, 1424, 1425, 1427, 1445, 1447, 1448, 1450, 1451, 1452, 1453, 1457, 1459, 1465, 1467, 1470, 1472, 1473, 1474, 1475, 1476, 1477, 1480, 1482, 1483, 1484, 1488, 1489, 1497, 1499, 1502, 1504, 1507, 1512, 1514, 1515, 1516, 1520, 1531, 1532, 1533, 1546, 1548, 1551, 1553, 1554, 1555, 1559, 1567, 1569, 1572, 1573, 1574, 1575, 1576, 1580, 1601, 1607, 1612, 1613, 1630, 1634, 1651, 1653, 1656, 1657, 1658, 1659, 1661, 1667, 1685, 1690, 1692, 1693, 1694, 1695, 1698, 1706, 1708, 1711, 1713, 1714, 1715, 1716, 1718, 1721, 1722, 1723, 1724, 1725, 1730, 1737, 1742, 1744, 1745, 1746, 1750, 1761, 1776, 1781, 1782, 1783, 1784, 1785, 1786, 1789, 1797, 1803, 1804, 1810, 1830, 1831, 1836, 1837, 1842, 1843, 1863, 1866, 1885, 1886, 1888, 1894, 1907, 1911, 1915, 1921, 1931, 1932, 1934, 1953, 1961, 1967 or 1971,

[0084] further more preferably compounds of Compounds No. 1, 2, 3, 4, 6, 8, 9, 11, 15, 17, 38, 40, 41, 42, 43, 47, 62, 63, 64, 72, 73, 74, 79, 87, 89, 92, 94, 97, 104, 106, 110, 121, 136, 143, 144, 145, 149, 157, 163, 164, 165, 166, 191, 197, 203, 220, 247, 248, 249, 251, 257, 282, 283, 284, 303, 312, 313, 314, 315, 334, 372, 373, 374, 375, 393, 394, 421, 427, 433, 471, 473, 474, 476, 477, 478, 479, 481, 485, 487, 505, 508, 510, 511, 512, 513, 517, 532, 533, 534, 535, 542, 543, 544, 549, 557, 558, 559, 562, 564, 567, 574, 576, 580, 591, 606, 613, 614, 615, 619, 627, 633, 634, 635, 636, 661, 667, 673, 690, 717, 718, 719, 721, 727, 752, 753, 754, 773, 782, 783, 784, 785, 804, 842, 843, 844, 845, 863, 864, 891, 897, 903, 941, 943, 944, 946, 948, 949, 951, 955, 957, 978, 980, 981, 982, 983, 987, 1002, 1003, 1004, 1012, 1013, 1014, 1019, 1027, 1029, 1032, 1034, 1037, 1044, 1046, 1050, 1061, 1076, 1083, 1084, 1085, 1089, 1097, 1103, 1104, 1105, 1106, 1131, 1137, 1143, 1160, 1187, 1188, 1189, 1191, 1197, 1222, 1223, 1224, 1243, 1252, 1253, 1254, 1255, 1274, 1312, 1313, 1314, 1315, 1333, 1334, 1361, 1367, 1373, 1411, 1413, 1414, 1416, 1418, 1419, 1421, 1425, 1427, 1448, 1450, 1451, 1452, 1453, 1457, 1472, 1473, 1474, 1482, 1483, 1484, 1489, 1497, 1499, 1502, 1504, 1507, 1514, 1516, 1520, 1531, 1546, 1553, 1554, 1555, 1559, 1567, 1573, 1574, 1575, 1576, 1601, 1607, 1613, 1630, 1657, 1658, 1659, 1661, 1667, 1692, 1693, 1694, 1713, 1722, 1723, 1724, 1725, 1744, 1782, 1783, 1784, 1785, 1803, 1804, 1831, 1837, 1843, 1885, 1886, 1894, 1907 or 1921.

[0085] It is particularly preferably mentioned

[0086] Compound No.1; [3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetic acid, Compound No.4; 3-{[3-[(E)-2-(6,7-difluoroquinolin-2-yl)-ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}-2-methyl-propionic acid, Compound No.8; 3-{[3-[(E)-2-(6,7-difluoroquinolin-2-yl)-ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid,

[0087] Compound No.9; 3-{[3-[(E)-2-(6,7-difluoroquinolin-2-yl)-ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}-2-methyl-propionic acid,

[0088] Compound No.471; [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)-ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetic acid,

[0089] Compound No.473; 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}propionic acid,

[0090] Compound No.474; 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cycloyhepten-5-yl]oxy}-2-methyl-propionic acid,

[0091] Compound No.476; [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thioacetic acid,

[0092] Compound No.477; 2-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid,

[0093] Compound No.478; 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid, Compound No.487; 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thiomethyl}-cyclopropane acetic acid,

[0094] Compound No.505; [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-yl]oxy-acetic acid,

[0095] Compound No.510; 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-yl]thio}-propionic acid,

[0096] Compound No.535; [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]oxy-acetic acid,

[0097] Compound No.542; 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]thio}-propionic acid,

[0098] Compound No.549; 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-8-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]thio}-propionic acid,

[0099] Compound No.557; [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-6-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]oxy-acetic acid,

[0100] Compound No.558; 2-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl)-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}propionic acid,

[0101] Compound No.559; 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-6-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}-propionic acid,

[0102] Compound No.562; [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-6-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]thio-acetic acid,

[0103] Compound No.564; 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-6-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]thio}-propionic acid,

[0104] Compound No.613; 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-trifluoromethyl-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid,

[0105] Compound No.718; 3-{[3-(7-chloro-6-fluoroquinolin-2-yl)methoxy-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid,

[0106] Compound No.1411; [3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetic acid,

[0107] Compound No.1416; [3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thioacetic acid,

[0108] Compound No.1418; 3-{[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid,

[0109] Compound No.1885; 3-{[3-[(E)-2-(5,6,7,8-tetrahydroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid or

[0110] Compound No.1921; 3-{[3-[(E)-2-(5,6,7,8-tetrahydroquinolin-2-yl)ethenyl]-9-trifluoromethyl-5H-dibenzo[a,d]cyclohepten-5-yl]thio} propionic acid.

[0111] The compound represented by the formula (I) of the present invention can be produced by, for example, Preparation process A, B, C, D, E or L shown below.

[0112] Preparation Process A

[0113] Preparation Process B

[0114] Preparation Process C

[0115] Preparation Process D

[0116] Preparation Process E

[0117] Preparation Process L

[0118] In the above reaction formulae, R¹, R², R³, A, B, X, Y, Z, m and n have the same meanings as defined above, L represents a halogen atom, a C₁-C₄ alkylsulfonyloxy group, a fluoro C₁-C₄ alkylsulfonyloxy group or a phenylsulfonyloxy group which may be substituted (said substituent is a C₁-C₄ alkyl group or a halogen atom), R⁴ representes a C₁-C₄ alkyl group or a phenyl group which may be substituted (said substituent is a C₁-C₄ alkyl group or a halogen atom), Tet represents a 1H-tetrazol-5-yl group, and Hal represents a halogen atom.

[0119] Preparation process A is a preparation process of Compound (I).

[0120] Step A1 of Preparation process A is a step of synthesizing Compound (III) by subjecting Compound (II) to halogenation or sulfonylation.

[0121] Halogenation of Compound (II) is carried out by reacting Compound (II) and a halogenating agent in a solvent or in the absence of a solvent (preferably in a solvent).

[0122] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, etc.; aromatic hydrocarbons such as benzene, toluene, etc.; or aliphatic hydrocarbons such as heptane, hexane, cyclohexane, etc., preferably halogenated hydrocarbons.

[0123] As the halogenating agent, there may be mentioned, for example, thionyl chloride, thionyl bromide, phosphorus oxychloride, phosphorus oxybromide, phosphorus pentachloride, etc., preferably thionyl chloride or phosphorus oxychloride. An amount of the halogenating agent to be used is usually 1 to 10-fold mol amount, preferably 1 to 2-fold mol amount based on the amount of Compound (II).

[0124] The reaction is carried out in the temperature range usually at −20 to 100° C., preferably at −10 to 30° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 5 minutes to 10 hours, preferably 10 minutes to 5 hours.

[0125] Sulfonylation of Compound (II) is carried out by reacting Compound (II) and a sulfonylating agent in the presence of a base in a solvent.

[0126] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, the same solvent as used in the above-mentioned halogenation reaction (for example, halogenated hydrocarbons, aromatic hydrocarbons or aliphatic hydrocarbons), etc., preferably halogenated hydrocarbons.

[0127] As the sulfonylating agent, there may be mentioned, for example, methanesulfonyl chloride, trifluoromethanesulfonyl chloride, methanesulfonic anhydride, trifluoromethanesulfonic anhydride, benzenesulfonyl chloride, toluenesulfonyl chloride, benzenesulfonyl bromide, toluenesulfonyl bromide, etc., preferably methanesulfonyl chloride, benzenesulfonyl chloride or toluenesulfonyl chloride. An amount of the sulfonylating agent to be used is usually 1 to 10-fold mol amount, preferably 1 to 3-fold mol amount based on the amount of Compound (II).

[0128] As the base, there may be mentioned, for example, amines such as triethylamine, tributylamine, diisopropylethylamine, pyridine, picoline, lutidine, 4-dimethylaminopyridine, etc., preferably triethylamine, diisopropylethylamine or pyridine. An amount of the base to be used is usually 1 to 10-fold mol amount, preferably 1 to 2-fold mol amount based on the amount of the sulfonylating agent.

[0129] The reaction is carried out in the temperature range usually at −10 to 100° C., preferably at 0 to 30° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 5 minutes to 10 hours, preferably 30 minutes to 5 hours.

[0130] Incidentally, Compound (III) can be separated and purified from the reaction mixture according to the usual method, but a crude product obtained by concentrating the reaction mixture can be used as such in the next step.

[0131] Step A2 is carried out by reacting Compound (III) and Compound (IV) in the presence or absence of a base in a solvent.

[0132] An amount of Compound (IV) to be used is usually 1 to 10-fold mol amount, preferably 1 to 5-fold mol amount based on the amount of Compound (III).

[0133] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, N,N-dimethylacetamide, hexamethylphosphoric acid triamide, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, 1,2-dichloroethane, etc.; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, etc.; nitrites such as acetonitrile, etc.; esters such as ethyl acetate, etc.; or ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane,. etc. or a mixed solvent of the above-mentioned solvents, preferably aprotic polar solvents, ethers or a mixed solvent of the above-mentioned solvents.

[0134] As the base to be used, there may be mentioned, for example, alkali metal hydrides such as sodium hydride, lithium hydride, etc.; alkali metal amides such as sodium amide, etc.; amines such as triethylamine, tributylamine, diisopropylethylamine, pyridine, picoline, lutidine, 4-dimethylaminopyridine, etc.; or alkali metal carbonates such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, etc., preferably amines or alkali metal hydrides. An amount of the base to be used may vary depending on the kinds of the starting compound(s), and it is usually 1 to 10-fold mol amount, preferably 1 to 5-fold mol amount based on the amount of Compound (IV). Incidentally, in the present reaction, the base may not necessarily be used.

[0135] The reaction is carried out in the temperature range usually at −50 to 150° C., preferably at −10 to 100° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 5 minutes to 10 hours, preferably 30 minutes to 5 hours.

[0136] Step A3 is a step of separately obtaining Compound (I), and it is suitably employed particularly when X is a sulfur atom. The present step is carried out by reacting Compound (II) and Compound (IV) in the presence of an acid catalyst in a solvent.

[0137] An amount of Compound (IV) to be used is usually 1 to 5-fold mol amount, preferably 1 to 2-fold mol amount based on the amount of Compound (II).

[0138] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, halogenated hydrocarbons such as methylene chloride, chloroform, 1,2-dichloroethane, etc.; alcohols such as methanol, ethanol, propanol, isopropanol, butanol, etc.; aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, N,N-dimethylacetamide, hexamethylphosphoric acid triamide, etc.; or ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, etc., preferably halogenated hydrocarbons.

[0139] As the acid catalyst to be used, there may be mentioned, for example, mineral acids such as hydrochloric acid, sulfuric acid, phosphoric acid, etc.; organic acids such as methanesulfonic acid, trifluoroacetic acid, etc.; Lewis acids such as boron trifluoride-diethyl ether complex, zinc chloride, tin tetrachloride, aluminum chloride, etc., preferably organic acids or boron trifluoride-diethyl ether complex. An amount of the catalyst to be used is usually 0.1 to 50-fold mol amount, preferably 1 to 10-fold mol amount based on the amount of Compound (II), and when the organic acids are used, it can be used with a markedly excessive amount also as a solvent.

[0140] The reaction is carried out in the temperature range usually at −10 to 100° C., preferably at 0 to 30° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 5 minutes to 10 hours, preferably 10 minutes to 5 hours.

[0141] Incidentally, in Compound (I), a compound wherein Z is a carboxyl group (Compound Ic mentioned below) can be directly produced by using Compound (IV) wherein Z is a carboxyl group, or can be synthesized, by using Compound (IV) wherein Z is a protected carboxyl group (the protective group is preferably a C₁-C₄ alkyl group), by once leading to Compound (I) wherein Z is a protected carboxyl group, and then, hydrolyzing the protective group under acidic or alkaline conditions by the conventional manner.

[0142] Also, in Compound (I), a desired protective group can be introduced into Compound (Ic) wherein Z is a carboxyl group according to the conventoinally known method (for example, see written by W.Greene and P. G. H. Wult, “Protective Group in Organic Synthesis” 2^(nd) Ed., John Wiley & Sons, p. 224).

[0143] Preparation process B is a preparation process of Compound (Ia) wherein X is a sulfur atom in Compound (I).

[0144] A reaction of obtaining Compound (VI) from Compound (II) or Compound (III) and a thiocarboxylic acid (V) in Step B1 can be carried out in the same manner as in the method described in Step A2 or Step A3 in the above-mentioned Preparation process A except for using a thiocarboxylic acid (V) in place of Compound (IV).

[0145] In Step B2, Compound (VII) can be synthesized by hydrolyzing Compound (VI) under alkaline conditions according to the conventional manner.

[0146] Step B3 is carried out by reacting Compound (VII) and Compound (VIII) in the presence of a base in a solvent. The present reaction can be carried out in the same manner as in the method described in the above-mentioned Step A2 except for using Compound (VII) in place of Compound (II), and using Compound (VIII) in place of Compound (IV).

[0147] An amount of Compound (VIII) to be used is usually 1 to 10-fold mol amount, preferably 1 to 5-fold mol amount based on the amount of Compound (VII).

[0148] Preparation process C is a preparation process of Compound (Ib) wherein Z is a 1H-tetrazole group in Compound (I), and in Step C1, a reaction of obtaining Compound (X) from Compound (II) or Compound (III) and Compound (IX) can be carried out in the same manner as in the method described in the above-mentioned Process A except for using Compound (IX) in place of Compound (IV).

[0149] In Step C2, Compound (Ib) can be synthesized by reacting Compound (X) and an azide compound in a solvent.

[0150] As the azide compound to be used, there may be mentioned, for example, alkali metal azides such as sodium azide, potassium azide, lithium azide, etc.; alkaline earth metal azides such as calcium azide, magnesium azide, etc.; or organic tin azides such as trimethyl tin azide, tributyl tin azide, triphenyl tin azide, etc. An amount of the azide compound to be used, it is usually 1 to 10-fold mol amount, preferably 1 to 5-fold mol amount based on the amount of Compound (X). In the reaction, the azide compound is used singly, or may be used in combination with, for example, Lewis acids such as aluminum chloride, stannic chloride, zinc chloride, titanium chloride, boron trifluoride-diethyl ether complex, etc.; ammonium salts such as ammonium chloride, tetramethylammonium chloride, etc.; sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, etc.; alkali metal chlorides such as lithium chloride, etc.; or amine salts such as triethylamine hydrochloride, etc.

[0151] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, aprotic polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone, N,N-dimethylacetamide, etc.; ethers such as tetrahydrofuran, dimethoxyethane, diethoxyethane, dioxane, etc.; aromatic hydrocarbons such as benzene, toluene, xylene, etc.; or aliphatic hydrocarbons such as hexane, petroleum ether, etc.

[0152] The reaction is carried out in the temperature range usually at 0 to 200° C., preferably 50 to 150° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 1 hour to 72 hours, preferably 3 hours to 48 hours.

[0153] Preparation process D is a preparation process of Compound (Id) wherein Z is a —CO—NH—SO₂-R³ group in Compound (I). Step D1 comprises a method of reacting Compound (Ic) and Compound (XI) in the presence of a condensing agent (Step D1a), or once leading Compound (Ic) to its reactive derivative (Step D1b), and then, reacting the reactive derivative and Compound (XI) in the presence of a base (Step D1c)

[0154] As the condensing agent to be used in Step D1a, there may be mentioned, for example, N,N′-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), N,N′-carbonyldiimidazol (CDI), diphenylphosphoric acid azide, hexafluorophosphoric acid benzotriazol-1-yloxy-tris-(dimethylamino)phosphonium (BOP), hexafluorophosphoric acid benzotriazol-1-yloxy-tris-pyrrolidinophosphonium (PyBOP), hexafluorophosphoric acid 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium (HBTU), tetrafluoroboric acid 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium (TBTU), etc., preferably DCC or EDC. An amount of the condensing agent to be used is usually 1 to 5-fold mol amount, preferably 1 to 3-fold mol amount based on the amount of Compound (Ic).

[0155] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, ethers such as diethyl ether, tetrahydrofuran, dimethoxyethane, diethoxyethane, dioxane, etc.; nitriles such as acetonitrile, etc.; aprotic polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone, N,N-dimethylacetamide, etc.; or halogenated hydrocarbons such as methylene chloride, chloroform, 1,2-dichloroethane, etc., and these can be used singly or as a mixed solvent.

[0156] The reaction is carried out in the temperature range usually at −20 to 100° C., preferably at 0 to 50° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 30 minutes to 24 hours, preferably 1 hour to 10 hours.

[0157] As the reactive derivative of Compound (Ic) in Step D1b, there may be mentioned, for example, acid halide derivatives of Compound (Ic) such as acid bromide compound or acid chloride compound of Compound (Ic); or reactive amide derivatives such as Compound (Ic) and imidazol, 3,5-dimethylpyrazol or triazole and Compound (Ic), etc., preferably acid halide derivative.

[0158] The acid halide compound of Compound (Ic) can be produced according to the conventional manner, and for example, it can be synthesized by reacting Compound (Ic) with a halogenating agent (for example, thionyl chloride, thionyl bromide, phosphorus pentachloride, etc.) in a solvent (for example, halogenated hydrocarbons such as methylene chloride, chloroform, 1,2-dichloroethane, etc.).

[0159] Also, reactive amide derivatives of Compound (IC) can be produced according to the conventional manner, and for example, in the case of an imidazolidated compound of Compound (Ic), it can be synthesized by reacting Compound (Ic) with 1,1′-carbonyldiimidazole in a solvent (for example, ethers such as diethyl ether, tetrahydrofuran, dimethoxyethane, diethoxyethane, dioxane, etc.; nitriles such as acetonitrile, etc.; aprotic polar solvents such as N,N-dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone, N,N-dimethylacetamide, etc.; or halogenated hydrocarbons such as methylene chloride, chloroform, 1,2-dichloroethane, etc.).

[0160] The reactive derivatives of Compound (Ic) can be used as such in the next Step D1c without separation after formation thereof.

[0161] Amounts of the reactive derivative of Compound (Ic) in Step D1c and Compound (XI) to be used in the reaction with Compound (XI) are each usually 1 to 10-fold mol amount, preferably 1 to 5-fold mol amount based on the amount of Compound (Ic).

[0162] As the base to be used, there may be mentioned, for example, amines such as triethylamine, tributylamine, diisopropylethylamine, pyridine, picoline, lutidine, 4-dimethylaminopyridine, 1,8-diazabicyclo[5.4.0]-7-undecene, 1,5-diazabicyclo[4.3.0]-5-nonene, etc., preferably triethylamine, tributylamine or diisopropylethylamine. An amount of the base to be used is usually 1 to 10-fold mol amount, preferably 1 to 5-fold mol amount based on the amount of Compound (Ic).

[0163] The reaction is carried out in the temperature range usually at 0 to 150° C., preferably at 10 to 100° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 5 minutes to 48 hours, preferably 30 minutes to 24 hours.

[0164] Also, Compound (Id) can be produced by a method which is through Compound (XII).

[0165] Step D2 is a step of obtaining Compound (XII) by amidating the carboxyl group of Compound (Ic), and can be carried out by optionally employing a method among the conventionally known methods. For example, Compound (XII) can be easily produced by reacting the above-mentioned reactive derivative of Compound (Ic) and ammonia.

[0166] Step D3 is carried out by reacting Compound (XII) and Compound (XIII) in the presence of a base in a solvent.

[0167] An amount of Compound (XIII) to be used is usually 1 to 10-fold mol amount, preferably 1 to 5-fold mol amount based on the amount of Compound (XII).

[0168] As the solvent and the base to be used, the same as those used in the above-mentioned Step D1 can be used, and the reaction can be carried out under the same conditions as those of Step D1.

[0169] Preparation process E is a preparation process of Compound (Ie) wherein Z is a —NH—SO₂—R³ group in Compound (I).

[0170] In Step E1, the reaction of obtaining Compound (XV) from Compound (II) or Compound (III) and Compound (XIV) can be carried out by the same method as those mentioned in the above-mentioned method A except for using Compound (XIV) in place of Compound (IV).

[0171] Step E2 is carried out by reacting Compound (XV) and Compound (XIII) in the presence of a base in a solvent.

[0172] An amount of Compound (XIII) to be used is usually 1 to 10-fold mol amount, preferably 1 to 5-fold mol amount based on the amount of Compound (XV).

[0173] As the solvent to be used, the same solvent as those mentioned in the above-mentioned Step D1 may be mentioned, and preferably halogenated hydrocarbons or aprotic polar solvents.

[0174] As the base to be used, the same base as those mentioned in the above-mentioned Step D1 may be mentioned, and an amount of the base to be used is usually 1 to 10-fold mol amount, preferably 1 to 5-fold mol amount based on the amount of Compound (XIV). Also, in the present reaction, the base may be used in an extremely excessive amount also as a solvent.

[0175] The reaction is carried out in the temperature range usually at −20 to 100° C., preferably at 0 to 50° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 5 minutes to 10 hours, preferably 30 minutes to 5 hours.

[0176] Preparation process L is a preparation process of Compound (If) wherein X is a methylene group and B is —CH═CH— in Compound (I), and Compound (Ig) wherein X is a methylene group and B is —CH₂O— in Compound (I).

[0177] Step L1 is carried out in the same manner as in Step F1 mentioned below except for using Compound (XXXVIII) in place of Compound (XVI), and Step L2 is carried out in the same manner as in Step F2 mentioned below except for using Compound (XXXIX) in place of Compound (XVII).

[0178] Step L3 is carried out in the same manner as in Step G1 of preparation process G mentioned below except for using Compound (XXXVIII) in place of Compound (XVI).

[0179] In the above-mentioned respective reactions, the formed objective Compound can be collected from the reaction mixture according to the conventional manner. For example, when insoluble materials are present, the objecttive compound can be obtained by, after removing the insoluble materials by filtration, removing the solvent, or by removing the solvent under reduced pressure, adding water to the residue, extracting the mixture with a water-immiscible organic solvent such as ethyl acetate, etc., if necessary, after drying over anhydrous sodium sulfate, etc., removing the solvent, and further, if necessary, by purifying with the conventional manner, for example, recrystallization, column chromatography, etc.

[0180] Also, the compound of the formula (I) of the present invention can be converted into a pharmaceutically acceptable salt by treating with an acid or a base according to the conventional manner. For example, in an inert solvent (preferably ethers such as diethyl ether, tetrahydrofuran, dimethoxyethane, diethoxyethane, dioxane, etc.; alcohols such as methanol, ethanol, propanol, isopropanol, butanol, etc.; halogenated hydrocarbons such as methylene chloride, chloroform, etc.; or water), it is reacted with a desired acid or a base, and the solvent is removed, or else, precipitated crystals are collected by filtration to obtain a desired salt. Also, it can be directly separated as a salt from the reaction mixture in the final reaction step.

[0181] Moreover, in the compound of the formula (I), there exist optical isomer(s) (including diastereomer) due to an asymmetric carbon(s) and/or geometric (E,Z) isomers due to an unsaturated carbon. These respective isomers can be separated by treating the corresponding racemic isomers or geometric isomer mixture by usual optical resolution methods (fractional recrystallization method, optical resolution column chromatography method or diastereomer method, etc.) or separation methods (recrystallization method, column chromatography method, etc.). For example, when optical isomers are to be separated, Compound (I) which is racemic mixture is reacted with an optically active sulfonic acid compound ((S) or (R)-camphor-10-sulfonic acid, etc.), to obtain one of the diastereomer salts, and if necessary, further subjecting to purification, the resulting diastereomer salt is resolved according to the conventional manner to obtain an optical isomer. Also, when the above reaction is carried out by using the starting compound which has been subjected to optical resolution or separation, a desired optical isomer or geometric isomer can be obtained.

[0182] Compound (IV), (V), (VIII), (IX), (XI), (XIII), (XIV) and other sub-starting materials which are used as starting materials in the above-mentioned Preparation process A, B, C, D, E or L are each well known compounds or can be easily produced according to the conventionally know method. Also, Compound (II) and (XXXVIII) can be produced by using either one of or in combination with two or more of Preparation processes F, G, H, I, J, K, N, O and P shown below optionally.

[0183] Preparation Process F

[0184] Preparation Process G

[0185] Preparation Process I

[0186] Preparation Process J

[0187] Preparation Process K

[0188] Preparation Process M

[0189] Preparation Process N

[0190] Preparation Process P

[0191] wherein R¹, R², A, Hal, m and n have the same meanings as defined above, Tf represents a trifluoromethanesulfonyl group, W represents a methoxy group or a halogen atom (preferably a bromine atom or an iodine atom), and R⁵ represents a C₁-C₄ alkyl group.

[0192] Preparation process F is a preparation process of Compound (IIa).

[0193] Step F1 is a step of synthesizing Compound (XVII) by trifrating Compound (XVI).

[0194] Trifration of Compound (XVI) is carried out by reacting Compound (XVI) and a trifrating agent in the presence of a base in a solvent.

[0195] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, etc.; aromatic hydrocarbons such as benzene, toluene, etc.; or aliphatic hydrocarbons such as heptane, hexane, cyclohexane, etc., preferably halogenated hydrocarbons.

[0196] As the trifrating agent, there may be mentioned, for example, trifluoromethanesulfonyl chloride or trifluoromethanesulfonic anhydride, preferably trifluoromethanesulfonic anhydride. An amount of the trifrating agent to be used is usually 1 to 10-fold mol amount, preferably 1 to 2-fold mol amount based on the amount of Compound (XVI).

[0197] As the base, there may be mentioned, for example, amines such as triethylamine, tributylamine, diisopropylethylamine, pyridine, picoline, lutidine, 4-dimethylaminopyridine, etc., preferably triethylamine, diisopropylethylamine or pyridine. An amount of the base to be used is usually 1 to 10-fold mol amount, preferably 1 to 2-fold mol amount based on the amount of the trifrating agent.

[0198] The reaction is carried out in the temperature range usually at −20 to 100° C., preferably at −10 to 30° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 5 minutes to 10 hours, preferably 30 minutes to 5 hours.

[0199] Step F2 is carried out by reacting Compound (XVII) and Compound (XVIII) in an inert gas atmosphere such as nitrogen, helium or argon in the presence of a catalyst (palladium catalyst) and a base, in a solvent.

[0200] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, etc., or acetonitrile, etc., preferably N,N-dimethylformamide.

[0201] As the base, there may be mentioned, for example, amines such as triethylamine, tributylamine, diisopropylethylamine, pyridine, picoline, lutidine, 4-dimethylaminopyridine, etc., preferably triethylamine. An amount of the base to be used is usually 1 to 10-fold mol amount, preferably 1 to 2-fold mol amount based on the amount of Compound (XVII).

[0202] Also, in place of the amines, quaternary amines such as tetrabutyl ammonium chloride, tetrabutyl ammonium bromide, etc., and alkali metal carbonates such as potassium carbonate, sodium carbonate, sodium hydrogen carbonate, etc. may be used in combination.

[0203] As the palladium catalyst, there may be mentioned, for example, palladium acetate, palladium acetate-triphenylphosphine, dichlorobis(triphenylphosphine)palladium, tetrakis(triphenylphosphine)palladium, etc., preferably palladium acetate-triphenylphosphine or tetrakis(triphenylphosphine)palladium. An amount of the palladium catalyst to be used is usually 0.01 to 1-fold mol amount, preferably 0.01 to 0.3-fold mol amount based on the amount of Compound (XVII).

[0204] Also, lithium chloride or lithium bromide may be co-present in the reaction.

[0205] The reaction is carried out in the temperature range usually at 0° C. to 200° C., preferably at 50° C. to 150° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 30 minutes to 48 hours, preferably 1 hour to 24 hours.

[0206] Reduction from Compound (XIX) to Compound (IIa) in Step F3 can be carried out by using a reducing agent in a solvent.

[0207] As the reducing agent, there may be mentioned, for example, sodium borohydride, lithium borohydride, sodium cyanoborohydride, lithium aluminum hydride, etc., preferably lithium borohydride.

[0208] The solvent to be used may be mentioned, for example, alcohols such as methanol, ethanol, propanol, butanol, etc.; ethers-such as tetrahydrofuran, dioxane, 1,2-dimethoxyethane, etc.; nitrites such as acetonitrile, etc.; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, etc.; water or a mixed solvent of the above-mentioned solvents, preferably tetrahydrofuran or a mixed solvent with tetrahydrofuran.

[0209] The reaction is carried out in the temperature range usually at −10 to 150° C., preferably at 0 to 100° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 10 minutes to 10 hours, preferably 30 minutes to 6 hours.

[0210] Step F4 is another process for producing Compound (XIX), and carried out in the similar conditions as those mentioned in the above-mentioned Step F2 by using Compound (XX) (preferably a bromine atom or an iodine atom as Hal) in place of Compound (XVII) as a starting compound.

[0211] Preparation process G is a preparation process of Compound (IIb).

[0212] Step G1 is carried out by reacting Compound (XVI) and Compound (XXI) in the presence of a base in a solvent, and carried out in the similar method as those mentioned in the above-mentioned Step A2 except for using Compound (XVI) in place of Compound (III), and using Compound (XXI) in place of Compound (IV).

[0213] Reduction from Compound (XXII) to Compound (IIb) in Step G2 is carried out in a solvent by using a reducing agent. It is carried out in the similar method as those mentioned in the above-mentioned Step F3 except for using Compound (XXII) in place of Compound (XIX).

[0214] Preparation process H is a preparation process of Compound (XXIX), and includes preparation processes of Compound (XX: W=a halogen atom) and a compound (XXXVI: W=methoxy group) mentioned below.

[0215] Preparation process H can be easily carried out by referring to the conventionally known method as disclosed in, for example, Helv. Chim. Acta, 48, 1240 (1965) or U.S. Pat. No. 1,207,404 B.

[0216] Step H1 is carried out by, for example, reacting Compound (XXIII) and Compound (XXIV) in the presence of a base such as sodium acetate in the absence of a solvent or using diphenyl ether as a solvent under heating (preferably at 100° C. to 250° C.) to carry out dehydration condensation.

[0217] A step of obtaining Compound (XXVI) by reducing Compound (XXV) in Step H2 is carried out by optionally employing a reducing method in which hydrogen is used in the presence of a Raney-nickel catalyst (U.S. Pat. No. 1,207,404 B) or a reducing method in which hydroiodic acid/red phosphorus are used (Helv. Chim. Acta, 48, 1240 (1965)), and when W is a halogen atom, the latter reduction method is suitably used.

[0218] A step of obtaining Compound (XXVII) by subjecting Compound (XXVI) to dehydration and cyclization in Step H3 is carried out by reacting Compound (XXVI) in a solvent or in the absence of a solvent, and in the presence of a catalyst (a dehydrating agent).

[0219] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, etc.; nitrobenzene, and carbon disulfide, preferably halogenated hydrocarbons.

[0220] As the catalyst to be used, there may be mentioned, for example, mineral acids such as sulfuric acid, phosphoric acid, polyphosphoric acid, etc.; acid anhydrides such as methanesulfonic anhydride, trifluoroacetic anhydride, etc.; Lewis acids such as boron trifluoride-diethyl ether complex, aluminum chloride, zinc chloride, etc., preferably polyphosphoric acid, methanesulfonic anhydride, trifluoroacetic anhydride or boron trifluoride-diethyl ether complex. Also, a mixture of trifluoroacetic anhydride and boron trifluoride-diethyl ether complex is suitably used. An amount of the catalyst to be used is usually 1 to 10-fold mol amount, preferably 1 to 5-fold mol amount based on the amount of Compound (XXVI).

[0221] The reaction is carried out in the temperature range usually at 0 to 150° C., preferably at 0 to 100° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 5 minutes to 10 hours, preferably 30 minutes to 5 hours.

[0222] For example, when polyphosphoric acid, etc. as the catalyst is used with a large amount, a solvent may not be specifically added. In this case, an amount thereof is 5 to 100-fold amount, preferably 10 to 30-fold amount by weight based on the amount of Compound (XXVI).

[0223] The reaction is carried out in the temperature range usually at 0 to 250° C., preferably at 100 to 200° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 10 minutes to 12 hours, preferably 30 minutes to 5 hours.

[0224] A step of obtaining Compound (XXVIII) by brominating Compound (XXVII) in Step H4 can be easily carried out by the conventionally known method, for example, in which reaction is carried out under irradiation of light using N-bromosuccineimide as a brominating agent, or reaction is carried out in the presence of a radical initiating agent such as azobisisobutyronitrile (AIBN), benzoyl peroxide (BPO), etc. The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, etc., preferably 1,2-dichloroethane.

[0225] When the reaction is carried out under irradiation of light, as a light source, a mercury lamp is suitably used. The N-bromosuccinimide to be-used is usually 1 to 2.5-fold mol amount, preferably 1 to 1.1-fold mol amount based on the amount of Compound (XXVII). A reaction temperature is usually in the range of 0 to 80° C., preferably 30 to 60° C.

[0226] A reaction time may vary depending on the reaction temperature and the like, and it is usually 1 hour to 12 hours, preferably 3 hours to 8 hours.

[0227] When the reaction is carried out in the presence of a radical initiator such as azobisisobutyronitrile (AIBN), benzoyl peroxide (BPO), etc., an amount of the radical initiator to be used is usually 0.001 to 0.1-fold mol amount, preferably 0.01 to 0.05-fold mol amount based on the amount of Compound (XXVII).

[0228] The N-bromosuccinimide to be used is usually 1 to 4-fold mol amount, preferably 1 to 1.1-fold mol amount based on the amount of Compound (XXVII).

[0229] The reaction is carried out in the temperature range usually at 50 to 100° C., preferably at 60 to 80° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 30 minutes to 12 hours, preferably 1 hour to 6 hours.

[0230] A step of obtaining Compound (XXIX) by removing hydrogen bromide from Compound (XXVIII) in Step H5 is carried out by treating Compound (XXVIII) with a base (preferably triethylamine or 1,5-diazabicyclo[4.3.0]-5-nonene (DBN)).

[0231] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, halogenated hydrocarbons such as dichloromethane, carbon tetrachloride, 1,2-dichloroethane, etc.; aromatic hydrocarbons such as benzene, toluene, xylene, etc.; esters such as methyl acetate, ethyl acetate, etc.; nitrites such as acetonitrile, propionitrile, etc., preferably 1,2-dichloroethane, toluene, ethyl acetate or acetonitrile.

[0232] An amount of the base to be used is 1 to 150-fold mol amount, preferably 1 to 15-fold mol amount based on the amount of Compound (XXVIII).

[0233] The reaction is carried out in the temperature range usually at 0 to 150° C., preferably at 60 to 120° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 30 minutes to 12 hours, preferably 1 hour to 3 hours.

[0234] Preparation process I is another process for producing Compound (XXVI) in Preparation process H.

[0235] Bromination reaction of Compound (XXX) in Step I1 is carried out in the same manner as in Step H4 except for using Compound (XXX) in place of Compound (XXVII).

[0236] Step I2 can be easily carried out by reacting Compound (XXXI) and triphenylphosphine in a solvent.

[0237] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, etc.; aromatic hydrocarbons such as benzene, toluene, xylene, etc.; esters such as methyl acetate, ethyl acetate, etc.; nitrites such as acetonitrile, propionitrile, etc.; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, etc., ketones such as acetone, methyl ethyl ketone, etc.; or dimethylsulfoxide, preferably ethyl acetate, or acetonitrile.

[0238] An amount of the triphenylphosphine to be used is 1 to 2-fold mol amount, preferably 1 to 1.5-fold mol amount based on the amount of Compound (XXXI).

[0239] The reaction is carried out in the temperature range usually at 0 to 150° C., preferably at 60 to 100° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 30 minutes to 12 hours, preferably 1 hour to 3 hours.

[0240] A reaction of Compound (XXXII) and Compound (XXXIII) in Step I3 is a reaction known as the so-called Wittig reaction, and carried out-optionally by selecting the conventionally known conditions.

[0241] An amount of Compound (XXXIII) to be used is usually 1 to 10-fold mol amount, preferably 1 to 1.5-fold mol amount based on the amount of Compound (XXXII).

[0242] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, halogenated hydrocarbons such as dichloromethane, carbon tetrachloride, chloroform, 1,2-dichloroethane, etc.; ethers such as diethyl ether, tetrahydrofuran, dioxane, dimethoxyethane, etc.; aromatic hydrocarbons such as benzene, toluene, xylene, etc.; esters such as methyl acetate, ethyl acetate, etc.; nitrites such as acetonitrile, propionitrile, etc.; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, etc.; dimethylsulfoxide or a mixed solvent of the above-mentioned solvents, and further, a mixed solvent of the above solvents and water may be also used.

[0243] The base to be used may include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide, etc.; alkali metal carbonates such as sodium carbonate, potassium carbonate, etc.; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, sodium t-butoxide, potassium t-butoxide, etc.; alkali metal hydrides such as sodium hydride, potassium hydride, etc.; alkyl lithium such as methyl lithium, butyl lithium, etc.; metal amides such as sodium amide, lithium diisopropyl amide, etc.; and organic amines such as triethylamine, diisopropylethylamine, tripropylamine, 1,5-diazabicyclo-[4.3.0]-5-nonene (DBN), etc. An amount of the base to be used is usually 1 to 5-fold mol amount, preferably 1 to 2-fold mol amount based on the amount of is Compound (XXXII).

[0244] The reaction is carried out in the temperature range usually at 0 to 150° C., preferably at 15 to 80° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 1 hour to 24 hours, preferably 1 hour to 6 hours.

[0245] Incidentally, in this step, a mixture of cis and trans geometric isomer can be usually obtained and it can be applied to the next step in the state of a mixture.

[0246] Hydrolysis reaction of Compound (XXXIV) to the carboxyl group in Step I4 may be also carried out, for example, by a typical alkali hydrolysis reaction using sodium hydroxide or potassium hydroxide, or a method disclosed in “Protective Group in Organic Synthesis” written by W. Greene and P. G. H. Wult, 2^(nd) Ed., John Wiley & Sons, p. 229.

[0247] Reduction of Compound (XXXV) in Step I5 can be carried out by a catalytic hydrogenation reaction or a reduction using hydroiodic acid/red phosphorus, and when W is a halogen atom, the reduction using hydroiodic acid/red phosphorus is suitable.

[0248] In the case of the catalytic hydrogenation reaction, Compound (XXXV) is subjected to catalytic reduction by hydrogen in the presence of a catalyst whereby Compound (XXVI) can be synthesized.

[0249] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, alcohols such as methanol, ethanol, etc., or ethers such as tetrahydrofuran, dioxane, etc., preferably alcohols.

[0250] As the catalyst to be used, there may be mentioned, for example, palladium-carbon, platinum-carbon, platinum black, rhodium-carbon or Raney nickel, preferably palladium-carbon.

[0251] In the catalytic hydrogenation reaction, a partial pressure of hydrogen is usually 1 atm. to 10 atm., preferably 1 atm. to 5 atm.

[0252] The reaction is carried out in the temperature range usually at 0° C. to 100° C., preferably at 20° C. to 80° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 15 minutes to 72 hours, preferably 30 minutes to 48 hours.

[0253] In the case of the reduction using hydroiodic acid/red phosphorus, the solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, water, acetic acid or propionic acid, preferably acetic acid. The hydroiodic acid to be used is 3 to 15-fold mol amount, preferably 4 to 8-fold mol amount based on 1 mol of Compound (XXXV).

[0254] The red phosphorus to be used is 1 to 10-fold mol amount, preferably 2 to 5-fold mol amount based on the amount of Compound (XXXV). A method of addition thereof may be once or divided into several times.

[0255] The reaction is carried out in the temperature range usually at 90 to 150° C., preferably at 100 to 130° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 1 hour to 48 hours, preferably 6 hours to 24 hours.

[0256] Preparation process J is a process for producing Compound (XVI) by demethylating Compound (XXXVI). Demethylation of Compound (XXXVI) is carried out by optionally employing a conventionally known method (see “Protective Group in Organic Synthesis” written by W.Greene and P. G. H. Wult, 2^(nd) Ed., John Wiley & Sons, p. 146), for example, a method of using hydrobromic acid or hydroiodic acid, or a method of using boron tribromide and trimethylsilane iodide, and the like.

[0257] Preparation process K is a preparation process of Compound (XVIII), and carried out easily by employing a conventionally known method, for example, a method as disclosed in J.Org.Chem., 61, 3398 (1996).

[0258] Preparation process M is another process for producing Compound (XXVI).

[0259] Step M1 is a process for producing Compound (XXXV′) by condensation reaction of Compound (XXX) and Compound (XXXIII) in the presence of a base.

[0260] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, alcohols such as methanol, ethanol, propanol, butanol, t-butanol, etc.; ethers such as tetrahydrofuran, dioxane, 1,2-dimethoxyethane, etc.; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, etc., preferably N,N-dimethylformamide.

[0261] An amount of Compound (XXXIII) to be used is usually 1 to 1.5-fold mol amount, preferably 1 to 1.2-fold mol amount based on the amount of Compound (XXX).

[0262] The base to be used may be mentioned alkali metal alkoxides such as sodium methoxide, sodium ethoxide, sodium t-butoxide, potassium t-butoxide, etc.; or alkali metal hydrides such as sodium hydride, potassium-hydride, etc., preferably sodium t-butoxide. An amount thereof to be used is usually 1 to 2-fold mol amount, preferably 1 to 1.5-fold mol amount based on the amount of Compound (XXX).

[0263] The reaction is carried out in the temperature range usually at 0 to 100° C., preferably at 10 to 40° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 1 to 24 hours, preferably 3 to 12 hours.

[0264] Step M2 is a hydrogenation reaction of olefin and can be carried out in the same manner as in Step I5 of Preparation process I.

[0265] Preparation process N is another process for producing Compound (XXIX).

[0266] Step N1 is a step of obtaining Compound (XXXX) by reacting Compound (XXVII) and N-bromosuccinimide under irradiation of light, preferably under irradiation of light using a mercury lamp light source.

[0267] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, etc., preferably 1,2-dichloroethane. An amount of the N-bromosuccinimide to be used is usually 1.8 to 2.5-fold mol amount, preferably 2.0 to 2.1-fold mol amount based on the amount of Compound (XXVII).

[0268] The reaction is carried out in the temperature range usually at 0 to 80° C., preferably at 30 to 60° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 1 hour to 12 hours, preferably 3 hours to 8 hours.

[0269] Step N2 is a step of converting from vicinal dibromide to olefin and is carried our easily by a method as disclosed in, for example, Synth., Comm., 26, 3791 (1996) or the like.

[0270] Preparation process O is a preparation process of an intermediate Compound (XXXXX) for the exemplary Compounds (If) and (Ig) wherein X=a methylene group among the compounds represented by the formula (I).

[0271] Step O1 is a step of producing Compound (XXXXIII) by reacting an acetylene compound (XXXXII) to Compound (XXXXI).

[0272] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be preferably mentioned, for example, ethers such as tetrahydrofuran, dioxane, 1,2-dimethoxyethane, etc.

[0273] An amount of the acetylene compound (XXXXII) to be used is usually 1 to 2-fold mol amount, preferably 1 to 1.5-fold mol amount based on the amount of Compound (XXXXI).

[0274] The reaction is carried out in the temperature range usually at 0 to 100° C., preferably at 0 to 30° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 5 minutes to 12 hours, preferably 30 minutes to 6 hours.

[0275] The reaction of producing Compound (XXXXIV) from Compound (XXXXIII) in Step O2 is carried out by subjecting to conversion reaction in a solvent in the presence of an acid catalyst.

[0276] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, alcohols such as methanol, ethanol, propanol, butanol, etc.; ethers such as tetrahydrofuran, dioxane, 1,2-dimethoxyethane, etc.; nitrites such as acetonitrile, etc.; and a mixed solvent of amides such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, etc. and water, preferably methanol, ethanol, tetrahydrofuran or a mixed solvent of N,N-dimethylformamide and water.

[0277] As the acid catalyst to be used, there may be mentioned, for example, mineral acids such as hydrochloric acid, sulfuric acid, phosphoric acid, etc.; or organic acids such as methanesulfonic acid, trifluoroacetic acid, etc., preferably trifluoroacetic acid. An amount of the catalyst to be used is usually 1 to 100-fold mol amount, preferably 1 to 50-fold mol amount based on the amount of Compound (XXXXIII).

[0278] The reaction is carried out in the temperature range usually at 0 to 100° C., preferably at 0 to 30° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 5 minutes to 48 hours, preferably 30 minutes to 24 hours.

[0279] Step O3 is a step of obtaining Compound (XXXXVI) by reacting Compound (XXXXIV) and Compound (XXXXV) in the presence of a base in a solvent.

[0280] An amount of Compound (XXXXV) to be used is usually 1 to 10-fold mol amount, preferably 1 to 5-fold mol amount based on the amount of Compound (XXXXIV).

[0281] As the base to be used, there may be mentioned, for example, alkali metal hydrides such as sodium hydride, lithium hydride, etc.; alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium t-butoxide, etc.; alkyl lithiums such as methyl lithium, butyl lithium, etc.; metal amides such as sodium amide, lithium diisopropyl amide, etc., preferably alkali metal hydride. An amount of the base to be used is usually 1 to 5-fold mol amount, preferably 1 to 2-fold mol amount based on the amount of Compound (XXXXV).

[0282] The solvent to be used is not specifically limited so long as it does not inhibit the reaction and can dissolve the starting materials with a certain extent, and there may be mentioned, for example, aromatic hydrocarbons such as benzene, toluene, etc.; ethers such as tetrahydrofuran, dioxane, dimethoxyethane, dimethoxyethane, etc.; or aprotic polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, etc., preferably ethers.

[0283] The reaction is carried out in the temperature range usually at −50° C. to 100° C., preferably at −10° C. to 50° C. A reaction time may vary depending on the reaction temperature and the like, and it is usually 15 minutes to 12 hours, preferably 30 minutes to 5 hours.

[0284] In Step O4, Compound (XXXXVII) can be synthesized by subjecting Compound (XXXXVI) to catalytic reduction with hydrogen in a solvent in the presence of a base, and the step is carried out in the same manner as in the catalytic hydrogenation of Step I5.

[0285] Step O5 is a conversion to olefin by dehydrogenation and, for example, it is carried out in the same manner as in the above-mentioned Preparation process N except for using Compound (XXXXVII) in place of Compound (XXVII).

[0286] Step O6 is demethylation of a methoxy group and hydrolysis of an ester group.

[0287] Demethylation of the methyl group and hydrolysis of the ester group are simultaneously accomplished by carrying out in the same manner as in, for example, Preparation process J except for using Compound (XXXXVIII) in place of Compound (XXXVI).

[0288] Step O7 is a protection step for a carboxyl group by esterification, and can be easily converted by a conventionally known method (for example, see “Protective Group in Organic Synthesis” written by W. Greene and P. G. H. Wult, 2^(nd) Ed., John Wiley & Sons, p. 224).

[0289] Preparation process P is another process for producing Compound (XVIII).

[0290] Step P1 is a step of producing Compound (XXXXXI) by reacting Compound (XXI) and triphenylphosphine, and Step P2 is a step of producing Compound (XVIII) by reacting Compound (XXXXXI) and formaldehyde in the presence of a base.

[0291] Step P1 is carried out in the same manner as in Step I2 except for using Compound (XXI) in place of Compound (XXXI).

[0292] Step P2 is carried out in the same manner as in Step I3 except for using Compound (XXXXXI) in place of Compound (XXXII), and using formaldehyde in place of Compound (XXXIII).

[0293] The compound represented by the present invention has a potent leukotriene antagonistic action, and extremely useful as an antiazma agent, an antiallergic agent and anti-inflammatory agent.

[0294] When used as a prophylactic or therapeutic medicament for the desiases described above, Compound (I) or a pharmaceutically acceptable salt thereof of the present invention can be administered alone or can be presented as part of a pharmaceutical formulation. The pharmaceutical formulation is prepared by blending the active ingredient with appropriate pharmaceutically acceptable excipient, diluent, etc., followed by formulation in the form of tablets, capsules, granules, powders or syrups, etc. for oral administration or in the form of injections, etc. for parenteral administration (preferably oral administration).

[0295] The production of such pharmaceutical formulation is carried out according to general technique known to those skilled in the art using additives such as an excipient (for example, a sugar derivative such as lactose, sucrose, glucose, mannitol, or sorbitol; a starch derivative such as corn starch, potato starch, α-starch, dextrin, or carboxymethyl starch; a cellulose derivative such as crystalline cellulose, low-substituted hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose, calcium carboxymethyl cellulose, or internally bridged sodium carboxymethyl cellulose; acacia; dextran; pullulan; a silicate derivative such as light silicic acid anhydride, synthetic aluminum silicate, or magnesium aluminate metasilicate; a phosphate derivative such as calcium phosphate; a carbonate derivative such as calcium carbonate; a sulfate derivative such as calcium sulfate; etc.), a binder (for example, one of the excipients described above; gelatin; polyvinylpyrrolidone; Macrogol (tradename), etc.), a disintegrator (for example, one of the excipients described above; a chemically modified starch, cellulose derivative such as sodium croscarmellose, sodium carboxymethyl starch; bridged polyvinylpyrrolidone, etc.), a lubricant (for example, talc; stearic acid; a metal salt of stearic acid such as calcium stearate, or magnesium stearate; colloidal silica; a wax such as bee gum and spermaceti; boric acid; glycol; a carboxylic acid such as fumaric acid, or adipic acid; a sodium carboxylate such as sodium benzoate; a sulfate such as sodium sulfate; leucine; a laurylsulfate such as sodium laurylsulfate, or magnesium laurylsulfate; a silicic acid such as silicic acid anhydride,or a silicic acid hydrate; one of the starch derivatives described above in relation to the excipient, etc.), a stabilizer (for example, a p-hydroxybenzoate derivative such as methylparaben, or propylparaben; an alcohol such as chlorobutanol, benzyl alcohol, or phenylethyl alcohol; benzalkonium chloride; a phenol derivative such as phenol, or cresol; thimerosal; acetic anhydride; sorbic acid, etc.), a corrigent (for example, a sweetening, souring, or flavoring agent, which are conventionally used, etc.), a diluent, a solvent for injection (for example, water, ethanol, glycerin, etc.), etc. A dose for administration may vary depending on symptom, an age, etc, and in the case of oral. administration, it is desirably administered 1 mg (preferably 5 mg) as a lower limit and 1000 mg (preferably 500 mg) as an upper limit once per day, and in the case of intravenous administration, it is desirably administered 0.1 mg (preferably 1 mg) as a lower limit and 500 mg (preferably 300 mg) as an upper limit once per day to an adult person with one to six times per day depending on the symptom.

[0296] Utilizability in Industry

[0297] The compound represented by the formula (I) or a pharmaceutically acceptable salt thereof according to the present invention has leukotriene C₄ antagonistic action and leukotriene E₄ antagonistic action in addition to potent leukotriene D₄ antagonistic action, and is extremely useful as an antiasthmatic agent, an antiallergic agent and an anti-inflammatory agent.

EXAMPLE

[0298] In the following, the present invention is explained by referring to Test examples and Examples, but the scope of the present invention is not limited to these.

[0299] Test Example 1

[0300] Leukotriene D₄ receptor binding test

[0301] <Preparation of Receptor Sample>

[0302] As a receptor sample, a lung cell membrane fraction from guinea pigs was used. Preparation of the membrane fraction was carried out according to the method of Ahn et al. (Eur. J. Pharmacol., 127, 153-155 (1986)). Lungs of Hartley male guinea pigs (400 to 500 g body weight, Japan SLC Inc.) were isolated, and perfused with a physiological saline, and then, adding 10 mM of PIPES, 10 mM of MgCl₂ and 10 mM of CaCl₂ buffer (pH 7.5) to the lung tissue and the mixture was homogenized. This homogenate was centrifuged at 70,000×g for 10 minutes to obtain a membrane fraction.

[0303] <Leukotriene D₄ Receptor Binding Test>

[0304] Leukotriene D₄ (LTD₄) receptor binding test was carried out according to the method of Aharony, et al. (J. Pharmacol. Expl. Ther., 243, 921-926 (1987)). To 0.42 mg of the receptor sample were added 10 mM of PIPES, 10 mM of MgCl₂ and 10 mM of CaCl₂ buffer (pH 7.5) to make the total amount of 480 μl, and 10 μl of [³H] LTD₄ (NEN Life Science Products Inc.) and 10 μl of a test compound in dimethylsulfoxide were added to the mixture, and the resulting mixture was incubated at 25° C. for 30 minutes. The mixtures thus incubated were filtered through a glass fiber filter (Whatman International Ltd., GF/C) using cell harvester (Biomedical Research & Development Laboratories, Inc., M-30R). The filter paper was washed with 10 mM of Tris and 100 mM of NaCl buffer (pH 7.5), and 5 ml of a liquid scintillator (nacalai tesque inc., clearsol I) was added thereto, and radioactivity was measured by a liquid scintillation analyzer (Packard Instrument Co., 2000CA). When a dissociation constant (Kd) of LTD₄ was to be obtained, [³H] LTD₄ with 0.03 to 0.5 nM was used, and 1 μM of non-radioactive LTD₄ was added. When a binding inhibition constant (Ki) of the Test compound is to be meaured, [³H] LTD₄ with 0.2 nM was used. Kd and Ki are calculated according to the method of Bennett et al. (Neurotransmitter Receptor Binding, 2^(nd) ed., edited by H.I. Yamamura et al., pp. 61-89, Raven Press (1985)). TABLE 2 Results of leukotriene D₄ receptor binding test Compound to be tested pKi Example Compound 3 10.0 Example Compound 4 9.7 Example Compound 7 9.7 Example Compound 9 9.8 Example Compound 10 10.0 Example Compound 11 9.9 Example Compound 12 9.7 Example Compound 13 9.9 Example Compound 17 9.8 Example Compound 29 9.6 Example Compound 30 9.7 Example Compound 31 9.7 Compound A 9.5

[0305] Compound A; 3-[2-(7-chloro-6-fluoroquinolin-2-yl)methoxy-6,11-dihydrobenz[b,e]oxepin-11-yl]thiopropionic acid (see WO 94/193445 publication)

Test Example 2

[0306] Leukotriene D₄ Induced Respiratory Constriction Test

[0307] Respiratory constriction was measured by modifying the method of Konzett and Rossler (Arch. Exp. Pathol. Pharmakol., 195, pp. 71-74 (1940)). Hartley male guinea pigs (400 to 500 g body weight, Japan SLC Inc.) were anesthetized with pentobarbital (50 mg/kg, s.c.), and a cannula was inserted into the trachea to carry out artificial ventilation with an artificial ventilator (manufactured by Harvard Apparatus, Model 683). An inner pressure of the respiratory tract was measured by a differential pressure transducer (Nihon Kohden, TP-603T) connected to the respiratory cannula and it is used as an index of respiratory constriction.

[0308] LTD₄ (0.03, 0.06, 0.13, 0.25, 0.5, 1 and 2 μg/kg, Simga-Aldrich) was intravenously administered from a cannula inserted into the right jugular vein from a low dose with an interval of 5 minutes to cause a respiratory constricttion reaction and an increased amount of a respiratory inner pressure was measured. Test compound was suspended in 0.5% sodium carboxymethyl cellulose aqueous solution or dissolved in 30% propylene glycol aqueous solution, and orally administered 24 hours before administration of LTD₄. Animals were fasted for 24 hours before administration of the Test compound. From a dose-reaction curve of LTD₄, 50% reaction dose (ED₅₀) was measured, and a dose of the Test compound required for shifting two-times of a dose-reaction curve of a control group to a higher dose side was calculated from the formula shown below and it was made as LTD₄ inhibitory activity. LTD₄ inhibitory activity =(Dose of Compound administered)/{(ED₅₀ of group to which Compound was added)/(ED₅₀ of control group)-1} TABLE 3 Results of leukotriene D₄ induced respiratory constriction test LTD₄ inhibitory Compound to be activity tested (μg/kg, p.o. 24 h) Example Compound 3 4.71 Example Compound 4 1.91 Example Compound 7 0.85 Example Compound 8 5.30 Example Compound 10 9.93 Example Compound 14 4.85 Example Compound 16 0.79 Example Compound 18 1.12 Example Compound 19 2.43 Example Compound 20 0.70 Example Compound 28 1.70 Compound A 25.52

[0309] Compound A; 3-[2-(7-chloro-6-fluoroquinolin-2-yl)-methoxy-6,11-dihydrobenz[b,e]oxepin-11-yl]thiopropionic acid (see WO 94/193445 publication)

Preparation Example 1

[0310] Tablet Compound of Example 7 30.0 mg Lactose 144.0 Corn starch 25.0 Magnesium stearate 1.0 200 mg

[0311] A tablet is prepared using the ingredients above. The components are blended and compressed by a tablet machine to form a tablet weighing 200 mg. The tablet may be coated if necessary, for example, to form a sugar-coated tablet or a coated tablet.

Example 1 Methyl[3-[(E)-2-(6,7-difluoroquinolin-2-yl)-ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetate (methyl ester of Exemplary Compound 1)

[0312] After a solution of 1.19 g (2.99 mmol) of 3-[(E)-2(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-ol dissolved in 10 ml of tetrahydrofuran was cooled to 0° C. with ice, 0.85 ml (5.98 mmol) of triethylamine and 0.30 ml (3.89 mmol) of methanesulfonyl chloride were added to the solution, and the mixture was stirred at 0° C. for 1 hour, and further at room temperature for 3 hours.

[0313] After completion of the reaction, the solvent was removed from the mixture under reduced pressure. The residue was dissolved in 15 ml of N,N-dimethylformamide, then, 0.54 g (5.98 mmol) of methyl glycolate was added to the mixture, and the resulting mixture was stirred at room temperature overnight.

[0314] After completion of the reaction, water was added to the reaction mixture, and extracted with chloroform. The organic layer was washed with water, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was applied to silica gel column chromatography (solvent: hexane/ethyl acetate=2/1 (volume ratio)) to obtain 0.38 g of the title compound as yellowish solid.

[0315] EI-MS (m/z) ; 469 (M⁺). CI-MS (m/z); 470 (M⁺+1).

Example 2 [3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetic acid (Exemplary Compound 1)

[0316] To mixed solution comprising 15 ml of methanol and 5 ml of tetrahydrofuran was dissolved 0.38 g (0.81 mmol) of methyl (3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetate, 2.4 ml (2.4 mmol) of an aqueous 1N sodium hydroxide solution was added to the solution and the resulting mixture was stirred at room temperature for 5 hours.

[0317] After completion of the reaction, the reaction mixture was adjusted to pH 6.5 by using an aqueous diluted acetic acid solution, and then, the mixture was concentrated under reduced pressure. Water was added to the residue, and the precipitated solid was collected by filtration. The solid was applied to silica gel column chromatography (solvent: chloroform/methanol=9/1 (volume ratio)) to obtain 0.21 g of the title compound as yellowish solid.

[0318] FAB-MS (m/z); 456 (M⁺+1). ¹H-NMR (δ, DMSO-d₆); 4.14 (s, 2H), 4.93 (s, 1H), 7.18-7.67 (m, 9H), 7.89-8.07 (m, 5H), 8.37 (d, J=8.5 Hz, 1H).

Example 3 Sodium [3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetate (sodium salt of Exemplary Compound 1)

[0319] In a mixed solution of 15 ml of tetrahydrofuran and 5 ml of methanol was dissolved 0.20 g (0.44 mmol) of [3[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo [s,d]-cyclohepten-5-yl]oxyacetic acid, 0.44 ml (0.44 mmol) of an aqueous 0.1N sodium hydroxide solution was added to the solution and the mixture was stirred at room temperature for 1 hour.

[0320] After completion of the reaction, the reaction mixture was concentrated, ethanol was added to the residue, and the precipitated solid was collected by filtration to obtain 0.14 g of the title compound as pale yellowish solid.

[0321] m.p.; 213 to 227° C. FAB-MS (m/z); 478 (M⁺+1). ¹H-NMR (δ, DMSO-d₆); 3.81 (s, 2H), 5.03 (s, 1H), 7.15-7.65 (m, 9H), 7.89-8.06 (m, 5H), 8.37 (d, J=8.8 Hz, 1H).

Example 4 Sodium 3-{[3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl[thio}propionate (sodium salt of Exemplary compound 8)

[0322] (a) In a mixed solution of 0.4 ml of trifluoroacetic acid and 40 ml of methylene chloride was dissolved 0.33 g (0.83 mmol) of 3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-ol, 0.08 ml (0.92 mmol) of 3-mercaptopropionic acid was added to the solution and the mixture was stirred at room temperature for 3 hours.

[0323] After completion of the reaction, the reaction mixture was concentrated, and the residue was applied to silica gel column chromatography (eluent: chloroform/methanol=19/1 (volume ratio)) to obtain 0.17 g (0.35 mmol) of 3-{[3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid as brown solid.

[0324] (b) 3-{[3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid obtained in Example 4(a) was dissolved as such in a mixed solution of 10 ml of tetrahydrofuran and 20 ml of methanol, 0.35 ml (0.35 mmol) of an aqueous 1N sodium hydroxide solution was added to the solution and the mixture was stirred at room temperature for 1 hour.

[0325] After completion of the reaction, the reaction mixture was concentrated, the residue was washed with diethyl ether, and dried under reduced pressure to obtain 0.14 g of the title compound as pale yellowish solid.

[0326] m.p.; 213 to 216° C. FAB-MS (m/z); 508 (M⁺+1). ¹H-NMR (δ, DMSO-d₆); 1.90-2.10 (m, 2H), 2.30-2.45 (m, 2H), 5.48 (s, 1H), 7.00 (s, 2H), 7.20-7.60 (m, 6H), 7.33 (d, J=8.8 Hz, 1H), 7.37 (d, J=7.3 Hz, 1H), 7.48 (d, J=8.5 Hz, 1H), 7.54 (d, J=16.4 Hz, 1H), 7.66 (d, J=7.8 Hz, 1H), 7.80-8.20 (m, 3 H), 7.87 (d, J=16.1 Hz, 1H), 8.04 (dd, J=9.0 Hz, 2.2 Hz, 1H), 8.38 (d, J=8.8 Hz, 1H).

[0327] Reaction was carried out in the same manner as in Example 4 to obtain compounds of the following Examples 5 to 9.

Example 5 Sodium 3-{[3-(7-chloro-6-fluoroquinolin-2-yl)methoxy-5H-dibenzo[a,d]cyclohepten-5-yl]thiol}propionate (sodium salt of Exemplary Compound 718)

[0328] Appearance; pale yellowish solid

[0329] m.p.; 229 to 232° C. ¹H-NMR (δ, DMSO-d₆); 2.00-2.20 (m, 2 H), 2.25-2.45 (m, 2 H), 5.38 (s, 1H), 5.41 (s, 2H), 6.83 (d, J=12.0 Hz, 1H), 6.90 (d, J=12.2 Hz, 1H), 7.00 (dd, J=8.5 Hz, 2.7 Hz, 1H), 7.20-7.55 (m, 6H), 7.75 (d, J=8.5 Hz, 1H), 8.05 (d, J=9.8 Hz, 1H), 8.29 (d, J=7.3 Hz, 1H), 8.44 (d, J=8.3 Hz, 1H).

Example 6 Sodium 3-{[3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}-2-(S)-methylpropionate (sodium salt of Exemplary Compound 9)

[0330] Appearance; pale yellowish solid

[0331] m.p.; 240 to 249° C. FAB-MS (m/z); 522(M⁺+1). ¹H-NMR (8, DMSO-d₆); 0.89 (d, J=6.6 Hz, 3 H), 2.10-2.89 (m, 2H), 2.51-2.58 (m, 1H), 5.45 (s, 1H), 7.00 (s, 2H), 7.31-7.49 (m, 5H), 7.54 (d, J=16.4 Hz, 1H), 7.66 (d, J=8.1 Hz, 1H), 7.85 (d, J=6.8 Hz, 1H), 7.86-7.98 (m, 2H), 7.98 (d, J=3.9 Hz, 1H), 8.04 (dd, J=11.0 Hz, 8.8 Hz, 1H), 8.38 (d, J=8.8 Hz, 1H).

Example 7 Sodium 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionate (sodium salt of Exemplary Compound 478)

[0332] Appearance; yellowish solid

[0333] m.p.; 228 to 238° C. FAB-MS (m/z); 524 (M⁺+1). ¹H-NMR (8, DMSO-d₆); 1.96-2.01 (m, 2H), 2.34-2.37 (m, 2H), 5.48 (s, 1H), 7.00 (s, 2H), 7.29-7.50 (m, 5H), 7.55 (d, J=16.4 Hz, 1H), 7.66 (dd, J=8.8 Hz, 1.5 Hz, 1H), 7.88 (d, J=16.4 Hz, 1H), 7.89 (d, J=1.5 Hz, 1H), 8.00 (d, J=8.8 Hz, 1H), 8.01 (d, J=10.0 Hz, 1H). 8.23 (d, J=7.1 Hz, 1H), 8.39 (d, J=8.5 Hz, 1H).

Example 8 Sodium 3-{(3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionate (sodium salt of Exemplary Compound 1418)

[0334] Appearance; orange solid

[0335] m.p.; 193 to 203° C. FAB-MS (m/z); 506 (M⁺+1). ¹H-NMR (δ, DMSO-d₆); 2.02-2.08 (m, 2H), 2.35-2.41 (m, 2H), 5.49 (s, 1H), 7.00 (s, 2H), 7.29-7.49 (m, 5H), 7.53-7.61 (m, 2H), 7.67 (d, J=8.1 Hz, 1H), 7.86-7.94 (m, 3 H), 7.99-8.03 (m, 2H), 8.41 (d, J=8.5 Hz, 1H).

Example 9 Sodium 3-{[3-[(E)-2-(5,6,7,8-tetrahydroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionate (sodium salt of Exemplary Compound 1885)

[0336] Appearance; pale yellowish solid

[0337] m.p.; 175 to 185° C. FAB-MS (m/z); 508 (M⁺+1). ¹H-NMR (δ, DMSO-d₆); 1.76-1.85 (m, 4 H), 2.08-2.13 (m, 2H), 2.35-2.40 (m, 2H), 2.74-2.84 (m, 4H), 5.44 (s, 1H), 6.97 (s, 2H), 7.28-7.46 (m, 8H), 7.54-7.59 (m, 2H), 7.78 (s, 1H).

[0338] Reaction was carried out in the same manner as in Examples 1 to 3 to obtain compounds of the following Examples 10 to 13.

Example 10 Sodium 3-{[3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}-2-(R)-methyl-propionate (sodium salt of Exemplary Compound 4)

[0339] Appearance; yellowish solid

[0340] 1H-NMR (δ, DMSO-d₆); 0.74, 1.20 (each b, 3H in total), 2.44 (b, 1H), 3.53, 3.77 (each b, 2H in total), 4.68, 5.55 (each s, 1H in total), 7.00-7.70 (m, 9H), 7.87-8.07 (m, 5H), 8.37 (d, J=8.8 Hz, 1H).

Example 11 Sodium [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetate (sodium salt of Exemplary Compound 471)

[0341] Appearance; yellowish solid ¹H-NMR (δ, DMSO-d₆); 3.81 (bs, 2H), 5.04 (bs, 1H), 7.15 (bs, 2H), 7.26-7.66 (m, 7H), 7.90-8.02 (m, 4H), 8.22 (d, J=7.3 Hz, 1H), 8.38 (d, J=8.6 Hz, 1H).

Example 12 Sodium 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}propionate (sodium salt of Exemplary Compound 473)

[0342] Appearance; yellowish solid ¹H-NMR (δ, DMSO-d₆); 2.37 (bs, 2H), 3.72, 3.82 (each bs, 2H in total), 4.70 (bs, 1H), 7.18 (bs, 2H), 7.28-7.66 (m, 8H), 7.88-8.04 (m, 4H), 8.27 (d, J=7.1 Hz, 1H), 8.38 (d, J=8.5 Hz, 1H).

Example 13 Sodium 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}-2-(R)-methylpropionate (sodium salt of Exemplary Compound 474)

[0343] Appearance; yellowish solid

[0344]¹H-NMR (δ, DMSO-d₆); 0.73, 1.20, 1.52 (each b, 3H in total), 2.45 (b, 1H), 3.33-3.86 (each m, 2H), 4.68, 5.55 (each s, 1H in total), 7.19-7.63 (m, 9H), 7.88-8.27 (m, 5H), 8.38 (d, J=8.8 Hz, 1H).

[0345] Reaction was carried out in the same manner as in Example 4 to obtain compounds of the following Examples 14 to 16.

Example 14 Sodium [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)-ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thioacetate (sodium salt of Exemplary Compound 476)

[0346] Appearance; orange solid

[0347]¹H-NMR (δ, DMSO-d₆); 2.61 (d, J=13.7 Hz, 2H), 2.66 (d, J=13.7 Hz, 2H), 5.63 (s, 1H), 6.98 (s, 2H), 7.31 (td, J=9.0 Hz, 2.0 Hz, 1H), 7.33-7.42 (m, 3H), 7.45 (d, J=7.8 Hz, 1H), 7.52 (d, J=16.4 Hz, 1H), 7.67 (dd, J=8.1 Hz, 1.5 Hz, 1H), 7.75 (d, J=2.0 Hz, 1H), 7.88 (d, J=16.1 Hz, 1H), 7.98 (d, J=9.8 Hz, 1H), 8.02 (d, J=10.0 Hz, 1H), 8.24 (d, J=7.6 Hz, 1H), 8.39 (d, J=8.6 Hz, 1H).

Example 15 Sodium 2-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionate (sodium salt of Exemplary Compound 477)

[0348] Appearance; pale yellowish solid

[0349]¹H-NMR (δ, DMSO-d₆); 1.10-1.14 (m, 3H), 2.68-2.76 (m, 3H), 5.67 (d, J=6.4 Hz, 1H), 6.98 (s, 2H), 7.23-7.54 (m, 6H), 7.67 (dd, J=8.1 Hz, 1.5 Hz, 1H), 7.31-7.90 (m, 2H), 7.98 (d, J=7.6 Hz, 1H), 8.01 (d, J=9.8 Hz, 1H), 8.23 (d, J=7.3 Hz, 1H), 8.39 (d, J=8.6 Hz, 1H).

Example 16 Sodium 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thiomethyl}-cyclopropaneacetate (sodium salt of Exemplary Compound 487)

[0350] Appearance; pale yellowish solid

[0351]¹H-NMR (δ, DMSO-d₆); 0.15 (bs, 2H), 0.33 (bs, 2H), 1.95 (d, J=14.2 Hz, 1H), 2.06 (d, J=14.2 Hz, 1H), 2.43 (d, J=13.4 Hz, 1H), 2.60 (d, J=13.4 Hz, 1H), 5.69 (s, 1H), 7.00 (s, 2H), 7.31 (td, J=7.3 Hz, 1.2 Hz, 1H), 7.34-7.42. (m, 2H), 7.45 (d, J=8.1 Hz, 1H), 7.55-7.61 (m, 2H), 7.66 (d, J=8.1 Hz, 1H), 7.88 (d, J=16.4 Hz, 1H), 7.96-8.03 (m, 3H), 8.26 (d, J=7.3 Hz, 1H), 8.39 (d, J=8.8 Hz, 1H).

[0352] Reaction was carried out in the same manner as in Examples 1 to 3 to obtain compounds of the following Example 17.

Example 17 Sodium [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-yl]oxy-acetate (sodium salt of Exemplary Compound 505)

[0353] Appearance; pale yellowish solid

[0354]¹H-NMR (δ, DMSO-d₆); 3.79 (bs, 2H), 5.08 (bs, 1H), 7.06-7.35 (m, 3H), 7.40-7.55 (m, 4H), 7.62-7.72 (m, 1H), 7.92-7.97 (m, 1H), 7.93 (d, J=16.4 Hz, 1H), 8.00 (d, J=9.8 Hz, 1H), 8.01 (d, J=8.5 Hz, 1H), 8.23 (d, J=7.3 Hz, 1H), 8.38 (d, J=8.8 Hz, 1H).

[0355] Reaction was carried out in the same manner as in Example 4 to obtain a compound of the following Example 18.

Example 18 Sodium 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-yl]thio}-propionate (sodium salt of Exemplary Compound 510)

[0356] Appearance; pale yellowish solid

[0357]¹H-NMR (δ, DMSO-d₆); 1.96-2.01 (m, 2H), 2.36-2.42 (m, 2H), 5.56 (s, 1H), 7.06-7.20 (m, 3H), 7.3.3 (d, J=6.6 Hz, 1H), 7.41 (td, J=13.4 Hz, 5.5 Hz, 1H), 7.47 (d, J=8.1 Hz, 1H), 7.55 (d, J=16.4 Hz, 1H), 7.67 (dd, J=9.4 Hz, 1.5 Hz, 1H), 7.83-7.89 (m, 2H), 7.96 (d, J=8.6 Hz, 1H), 8.01 (d, J=9.7 Hz, 1H), 8.21 (d, J=7.3 Hz, 1H), 8.38 (d, J=8.8 Hz, 1H).

[0358] Reaction was carried out in the same manner as in Examples 1 to 3 to obtain a compound of the following Example 19.

Example 19 Sodium [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-chloro-5H-dibenzo[a,d]cyclohepten-5yl]oxy-acetate (sodium salt of Exemplary Compound 535)

[0359] Appearance; pale yellowish solid

[0360]¹H-NMR (δ, DMSO-d₆); 3.79 (s, 2H), 5.07 (s, 1H), 7.35-7.51 (m, 6H), 7.66 (bs, 2H), 7.90-8.03 (m, 4H), 8.23 (d, J=7.3 Hz, 1H), 8.38 (d, J=8.5 Hz, 1H).

[0361] Reaction was carried out in the same manner as in Example 4 to obtain compounds of the following Examples 20 to 21.

Example 20 Sodium 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-chloro-5H-dibenzo[a,d]cyclohepten-5yl]thio}-propionate (sodium salt of Exemplary Compound 542)

[0362] Appearance; yellowish solid

[0363]¹H-NMR (δ, DMSO-d₆); 1.97-2.09 (m, 2H), 2.41-2.46 (m, 2H), 5.56 (s, 1H), 7.20 (d, J=12.5 Hz, 1H), 7.26 (d, J=12.5 Hz, 1H), 7.36-7.52 (m, 4H), 7.56 (d, J=16.4 Hz, 1H), 7.69 (dd, J=8.1 Hz, 1.5 Hz, 1H), 7.88 (d, J=16.4 Hz, 1H), 7.91 (d, J=1.5 Hz, 1H), 7.98 (d, J=8.8 Hz, 1H), 8.02 (d, J=9.8 Hz, 1H), 8.23 (d, J=7.3 Hz, 1H), 8.40 (d, J=8.6 Hz, 1H).

Example 21 Sodium 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-8-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]thio}-propionate (sodium salt of Exemplary Compound 549)

[0364] Appearance; yellowish solid

[0365]¹H-NMR (δ, DMSO-d₆); 1.96-2.01 (m, 2H), 2.35-2. 40 (m, 2H), 5.54 (s, 1H), 6.98 (d, J=12.0 Hz, 1H), 7.07 (d, J=12.2 Hz, 1H), 7.43 (dd, J=8.3 Hz, 2.2 Hz, 1H), 7.47 (d, J=8.1 Hz, 1H), 7.50-7.58 (m, 2H), 6.68 (d, J=7.8 Hz, 1H), 7.84-7.90 (m, 2H), 7.98 (d, J=8.8 Hz, 1H), 8.02 (d, J=9.8 Hz, 1H), 8.02 (d, J=7.8 Hz, 1H), 8.39 (d, J=8.8 Hz, 1H).

[0366] Reaction was carried out in the same manner as in Examples 1 to 3 to obtain compounds of the following Examples 22 to 25.

Example 22 Sodium [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-6-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]oxy-acetate (sodium salt of Exemplary Compound 557)

[0367] Appearance; pale yellowish solid

[0368]¹H-NMR (δ, DMSO-d₆); 3.06 (d, J=15.0 Hz, 1H), 3.12 (d, J=15.0 Hz, 1H), 6.52 (s, 1H), 7.07 (d, J=12.0 Hz, 1H), 7.11 (d, J=12.5 Hz, 1H), 7.36 (t, J=7.8 Hz, 1H), 7.48-7.58 (m, 4H), 7.78-7.82 (m, 2H), 7.94 (d, J=16.4 Hz, 1H), 7.99-8.02 (m, 2H), 8.22 (d, J=7.3 Hz, 1H), 8.39 (d, J=8.8 Hz, 1H).

Example 23 Sodium 2-(R)-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}propionate (sodium salt of Exemplary Compound 558).

[0369] Appearance; yellowish solid

[0370]¹H-NMR (δ, DMSO-d₆); 0.84-0.86, 1.46-1.50 (each m, 1H in total), 3.00-3.04, 3.75-3.79 (each m, 1H in total), 5.01, 5.95 (each s, 1H in total), 7.03, 7.15 (each s, 1H in total), 7.20-8.01 (m, 11H), 8.04 (d, J=10.0 Hz, 1H), 8.23 (d, J=7.3 Hz, 1H), 8.37 (dd, J=8.8 Hz, 2.4 Hz, 1H)

Example 24 Sodium 2-(S)-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}propionate (sodium salt of Exemplary Compound 558)

[0371] Appearance; pale yellowish solid

[0372]¹H-NMR (δ, DMSO-d₆); 0.82-0.84, 1.44-1.48 (each m, 1H in total), 3.33-3.42, 3.69-3.78 (each m, 1H in total), 5.00, 5.94 (each s, 1H in total), 7.03, 7.15 (each s, 1H in total), 7.20-7.99 (m, 11H), 8.04 (d, J=10.0 Hz, 1H), 8.23 (d, J=7.3 Hz, 1H), 8.37 (dd, J=8.8 Hz, 2.4 Hz, 1H).

Example 25 Sodium 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-6-chloro-5H-dibenzo[a,d]cyclopheten-5-yl]oxy}-propionate (sodium salt of Exemplary Compound 559)

[0373] Appearance; pale yellowish solid

[0374]¹H-NMR (δ, DMSO-d₆); 1.86-1.92 (m, 2H), 3.09-3.22 (m, 2H), 6.26 (s, 1H), 7.08 (d, J=12.0 Hz, 1H), 7.13 (d, J=12.2 Hz, 1H), 7.38 (t, J=7.6 Hz, 1H), 7.51 (dd, J=7.8 Hz, 1.2 Hz, 1H), 7.53-7.62 (m, 3H), 7.80 (dd, J=8.1 Hz, 1.5 Hz, 1H), 7.92 (s, 1H), 7.95 (d, J=16.4 Hz, 1H), 7.99-8.03 (m, 2H), 8.22 (d, J=7.3 Hz, 1H), 8.39 (d, J=8.5 Hz, 1H).

[0375] Reaction was carried out in the same manner as in Example 4 to obtain compounds of the following Examples 26 to 28.

Example 26 Sodium [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-6-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]thio-acetate (sodium salt of Exemplary Compound 562)

[0376] Appearance; orange solid

[0377]¹H-NMR (δ, DMSO-d₆); 2.77 (d, J=13.4 Hz, 1H), 2.85 (d, J=13.7 Hz, 1H), 6.17 (s, 1H), 7.04 (d, J=12.0 Hz, 1H), 7.08 (d, J=12.0 Hz, 1H), 7.30 (t, J=7.8 Hz, 1H), 7.41 (d, J=7.1 Hz, 1H), 7.47-7.58 (m, 3H), 7.72 (d, J=8.1 Hz, 1H), 7.79 (s, 1H), 7.91 (d, J=16.4 Hz, 1H), 7.98-8.03 (m, 2H), 8.22 (d, J=7.7 Hz, 1H), 8.39 (d, J=8.8 Hz, 1H).

Example 27 Sodium 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-6-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]thio}-propionate (sodium salt of Exemplary Compound 564)

[0378] Appearance; yellowish solid

[0379]¹H-NMR (δ, DMSO-d₆); 1.93-2.07 (m, 2H), 2.49-2.55 (m, 2H), 6.02 (s, 1H), 7.06 (d, J=12.2 Hz, 1H), 7.11 (d, J=12.0 Hz, 1H), 7.32 (t, J=7.6 Hz, 1H), 7.42 (dd, J=7.8 Hz, 1.2 Hz, 1H), 7.51 (d, J=8.1 Hz, 1H), 7.52-7.62 (m, 2H), 7.75 (dd, J=8.1 Hz, 1.5 Hz, 1H), 7.82 (d, J=1.5 Hz, 1H), 7.92 (d, J=16.4 Hz, 1H), 7.99-8.03 (m, 2H), 8.22 (d, J=7.3 Hz, 1H), 7.39 (d, J=8.8 Hz, 1H).

Example 28 Sodium 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-trifluoromethyl-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionate (sodium salt of Exemplary Compound 613)

[0380] Appearance; pale yellowish solid

[0381] FAB-MS (m/z): 492 (M⁺+1).

[0382]¹H-NMR (δ, DMSO-d₆); 1.99-2.09 (m, 2H), 2.43-2.53 (m, 2H), 5.65 (s, 1H), 7.69-7.30 (m, 2H), 7.50-7.59 (m, 3H), 7.67-7.74 (m, 2H), 7.85-8.03 (m, 5H), 8.23 (d, J=7.3 Hz, 1H), 8.40 (d, J=8.8 Hz, 1H).

[0383] Reaction was carried out in the same manner as in Examples 1 to 3 to obtain a compound of the following Example 29.

Example 29 Sodium [3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetate (sodium salt of Exemplary Compound 1411)

[0384] Appearance; orange solid

[0385]¹H-NMR (δ, DMSO-d₆); 3.80 (bs, 2H), 5.04 (bs, 1H), 7.16 (bs, 2H), 7.27-7.66 (m, 8H), 7.92-8.02 (m, 4H), 8.04 (d, J=2.2 Hz, 1H), 8.40 (d, J=8.5 Hz, 1H).

[0386] Reaction was carried out in the same manner as in Example 4 to obtain compounds of the following Examples 30 to 31.

Example 30 Sodium [3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thioacetate (sodium salt of Exemplary Compound 1416)

[0387] Appearance; pale yellowish solid

[0388] FAB-MS (m/z); 492 (M⁺+1). ¹H-NMR (δ, DMSO-d₆); 2.65 (d, J=13.9 Hz, 2H), 2.68 (d, J=13.9 Hz, 2H), 5.64 (s, 1H), 6.98 (s, 2H), 7.22-7.46 (m, 5H), 7.53 (d, J=16.4 Hz, 1H), 7.59 (dd, J=8.8 Hz, 2.2 Hz, 1H), 7.67 (dd, J=8.1 Hz, 1.5 Hz, 1H), 7.77 (d, J=1.5 Hz, 1H), 7.87-8.04 (m, 4H), 8.41 (d, J=8.5 Hz, 1H).

Example 31 Sodium 3-{[3-[(E)-2-(5,6,7,8-tetrahydroquinolin-2-yl)ethenyl]-9-trifluoromethyl-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionate (sodium salt of Exemplary Compound 1921)

[0389] Appearance; pale yellowish solid

[0390] FAB-MS (m/z): 544 (M⁺+1). ¹H-NMR (δ, DMSO-d₆); 1.75-1.85 (m, 4H), 2.00-2.05 (m, 2H), 2.42-2.47 (m, 2H), 2.72-2.87 (m, 4H), 5.60 (s, 1H), 7.14-7.32 (m, 4H), 7.44-7.47 (m, 2H), 7.53-7.61 (m, 3H), 7.72 (d, J=7.6 Hz, 1H), 7.81-7.83 (m, 2H).

Reference Example 1 (a) 7-Chloro-2-vinyl quinolin

[0391] The title compound was obtained by the method as described in J. Org. Chem., 61, 3398 (1996).

[0392] Appearance; ocherous solid

[0393]¹H-NMR (δ, DMSO-d₆); 5.69 (dd, J=11.0 Hz, 1.0 Hz, 1H), 6.31 (dd, J=17.6 Hz, 0.7 Hz, 1H), 7.00 (dd, J=17.8 Hz, 11.0 Hz, 1H), 7.45 (dd, J=8.8 Hz, 2.0 Hz, 1H), 7.60 (d, J=8.5 Hz, 1H), 7.71 (d, J=8.5 Hz, 1H), 8.06-8.10 (m, 2H).

(b) 3-Trifluoromethanesulfonyloxy-5H-dibenzo[a,d]-cyclohepten-5-one

[0394] In 30 ml of methylene chloride was dissolved 0.23 g (1.0 mmol) of 3-hydroxy-5H-dibenzo[a,d]cyclohepten-5-one and after cooling the solution with ice-water, 0.33 ml (2.0 mmol) of trifluoromethanesulfonic anhydride and 0.27 ml (2.0 mmol) of triethylamine were added to the solution and the resulting mixture was stirred under ice-cooling for 4 hours.

[0395] After completion of the reaction, the reaction mixture was concentrated, and the residue was applied to silica gel column chromatography (eluent: chloroform) to obtain 0.30 g of the title compound as brown oily product.

[0396] CI-MS (m/z); 355 (M⁺+1). EI-MS; 354 (M⁺). ¹H-NMR (δ, DMSO-d₆); 7.31 (d, J=12.2 Hz, 1H), 7.37 (d, J=12.2 Hz, 1H), 7.50-8.40 (m, 7H).

(c) 3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-one

[0397] In 30 ml of N,N-dimethylformamide were dissolved 0.89 g (2.5 mmol) of 3-trifluoromethanesulfonyloxy-5H-dibenzo[a,d]cyclohepten-5-one and 0.48 g (2.5 mmol) of 7-chloro-2-vinyl quinoline, and then, 100 mg (0.5 mmol) of palladium acetate, 420 mg (1.6 mmol) of triphenylphosphine and 2.1 g (24 mmol) of lithium bromide were added to the mixture and the atmosphere thereof was made nitrogen. Then, 5.0 ml (36 mmol) of triethylamine was added to the mixture, and the resulting mixture was stirred under nitrogen atmosphere at 120° C. for 10 hours.

[0398] After completion of the reaction, the reaction mixture was concentrated, and the residue was applied to silica gel column chromatography (eluent: toluene/ethyl acetate=9/1 (volume ratio)) to obtain 0.53 g of the title compound as pale brown solid.

[0399] CI-MS (m/z) ; 394 (M⁺+1)

[0400]¹H-NMR (δ, DMSO-d₆); 7.28 (s, 2H), 7.59-7.69 (m, 3H), 7.78-7.83 (m, 3H), 7.97-8.06 (m, 4H), 8.13-8.20 (m, 2H), 8.38 (s, 1H), 8.44 (d, J=9.3 Hz, 1H).

(d) 3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-ol

[0401] In a mixed solution of 40 ml of tetrahydrofuran and 10 ml of methanol was dissolved 0.53 g (1.3 mmol) of 3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]-5H-debenxo[a,d]-cyclohepten-5-one, and 0.11 g (2.6 mmol) of sodium borohydride was added to the mixture and the resulting mixture was stirred at room temperature for 3 hours.

[0402] After completion of the reaction, water was added to the reaction mixture, a pH of the mixture was adjusted to about 2.0 with 1N hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated. The residue was dried under reduced pressure to obtain 0.33 g of the title compound as ocherous solid.

[0403] CI-MS (m/z); 396 (M⁺+1).

[0404]¹H-NMR (δ, DMSO-d₆); 5.10 (d, J=3.4 Hz, 1H), 6.20 (s, 1H), 7.18 (s, 2H), 7.26 (td, J=8.8 Hz, 1.2 Hz, 1H), 7.37-7.52 (m, 4H), 7.59 (dd, J=8.5 Hz, 2.2 Hz, 1H), 7.64 (dd, J=8.1 Hz, 1.7 Hz, 1H), 7.76 (d, J=7.6 Hz, 1H), 7.91-8.04 (m, 5H), 8.40 (d, J=8.3 Hz, 1H).

Reference Example 2

[0405] Reaction was carried out in the same manner as in Reference Example 1(a) to obtain a compound of the following Reference Example 2(a).

(a) 7-Chloro-6-fluoro-2-vinylquinoline

[0406] Appearance; yellowish solid

[0407] CI-MS (m/z); 208 (M⁺+1). EI-MS; 207 (M⁺). ¹H-NMR (δ, DMSO-d₆) ; 5.73 (dd, J=11.0 Hz, 1.0 Hz, 1H), 6.43 (dd, J=17.6 Hz, 1.0 Hz, 1H), 6.98 (dd, J=17.8 Hz, 11.0 Hz, 1H), 7.89 (d, J=8.8 Hz, 1H), 8.01 (d, J=9.8 Hz, 1H), 8.21 (d, J=7.3 Hz, 1H). 8.37 (d, J=9.0 Hz, 1H).

[0408] Reaction was carried out in the same manner as in Reference Example 1(c) to obtain a compound of the following Reference Example 2(b).

(b) 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyI]-5H-dibenzo[a,d]cyclohepten-5-one

[0409] Appearance; pale yellowish solid

[0410]¹H-NMR (δ, DMSO-d₆); 7.29 (s, 2H), 7.63-7.70 (m, 2H), 7.78-7.84 (m, 3H), 8.00-8.05 (m, 3H), 8.13-8.21 (m, 2H), 8.23 (d, J=7.6 Hz, 1H), 8.38 (d, J=1.7 Hz, 1H), 8.42 (d, J=9.3 Hz, 1H).

[0411] Reaction was carried out in the same manner as in Reference Example 1(d) to obtain a compound of the following Reference Example 2(c).

(c) 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-ol

[0412] Appearance; yellowish solid

[0413]¹H-NMR (δ, DMSO-d₆); 5.09 (d, J=3.9 Hz, 1H), 6.20 (s, 1H), 7.18 (s, 2H), 7.26 (td, J=7.3 Hz, 1.2 Hz, 1H), 7.37-7.50 (m, 4H), 7.60 (d, J=7.6 Hz, 1H), 7.63 (dd, J=7.8 Hz, 1.7 Hz, 1H), 7.93 (d, J=16.4 Hz, 1H), 7.98-8.02 (m, 3H), 8.21 (d, J=7.3 Hz, 1H), 8.38 (d, J=8.5 Hz, 1H).

Reference Example 3

[0414] Reaction was carried out in the same manner as in Reference Example 1(a) to obtain a compound of the following Reference Example 3(a).

(a) 6,7-Difluoro-2-vinylquinoline

[0415] Appearance; pale yellowish solid

[0416] CI-MS (m/z); 192 (M⁺+1). EI-MS; 191 (M⁺). ¹H-NMR (δ, DMSO-d₆); 5.69 (dd, J=11.0 Hz, 1.0 Hz, 1H), 6.39 (dd, J=17.6 Hz, 1.0 Hz, 1H), 6.93 (dd, J=8.1 Hz, 3.9 Hz, 1H), 6.95 (dd, J=17.6 Hz, 11.0 Hz, 1H), 7.82 (d, J=8.8 Hz, 1H), 8.00 (dd, J=9.0 Hz, 2.2 Hz, 1H), 8.33 (d, J=8.5 Hz, 1H).

[0417] Reaction was carried out in the same manner as in Reference Example 1(c) to obtain a compound of the following Reference Example 3(b).

(b) 3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-one

[0418] Appearance; brown solid

[0419] CI-MS (m/z); 396 (M⁺+1). EI-MS; 395 (M⁺). ¹H-NMR (δ, DMSO-d₆); 7.29 (s, 2H), 7.50-7.90 (m, 7H), 7.95-8.30 (m, 5H), 8.41 (d, J=8.5 Hz, 1H).

[0420] Reaction was carried out in the same manner as in Reference Example 1(d) to obtain a compound of the following Reference Example 3(c).

(c) 3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-ol

[0421] Appearance; brown solid

[0422] CI-MS (m/z) ; 398 (M⁺+1) EI-MS; 397 (M⁺). ¹H-NMR (δ, DMSO-d₆); 5.09 (s, 1H), 7.18 (s, 2H), 7.20-7.70 (m, 2H), 7.28 (d, J=7.3 Hz, 1H), 7.38 (d, J=7.6 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.49 (d, J=7.6 Hz, 1H), 7.76 (d, J=7.6 Hz, 1H), 7.80-8.20 (m, 4H), 7.93 (d, J=16.6 Hz, 1H), 8.36 (d, J=8.5 Hz, 1H).

Reference Example 4 (a) 5,6,7,8-Tetrahydro-2-vinylquinoline

[0423] In 300 ml of acetonitrile was dissolved 14.7 g (65 mmol) of (5,6,7,8-tetrahydroquinolin-2-yl)methyl bromide, and 25.5 g (97.5 mmol) of triphenylphosphine was added to the mixture and the resulting mixture was refluxed for 2 hours. After cooling the mixture with an ice-bath, precipitates were collected by filtration and washed with diethyl ether to obtain (5,6,7,8-tetrahydroquinolin-2-yl)methyltriphenylphosphonium bromide as pale yellowish solid. Then, the obtained solid was dissolved in 250 ml of chloroform, 9.50 g (117 mmol) of 37% formaldehyde and 8.10 g (76 mmol) of an aqueous sodium carbonate solution (20 ml) were added to the solution and the mixture was stirred at room temperature for 2 hours.

[0424] After completion of the reaction, water was added to the reaction mixture and the mixture was extracted with chloroform. The organic layer was dried over potassium carbonate and concentrated. The residue was applied to silica gel column chromatography (eluent: hexane/ethyl acetate=9/1 (volume ratio)) to obtain 6.01 g of the title compound as yellowish oily product.

[0425] CI-MS (m/z) ; 160 (M⁺+1) EI-MS; 159 (M⁺). ¹H-NMR (δ, CDCl₃); 1.85 (m, 4H), 2.75 (dd, J=17.6 Hz, 1.0 Hz, 2H), 2.91 (dd, J=8.1 Hz, 3.9 Hz, 2H), 5.41 (dd, J=10.7 Hz, 1.2 Hz, 1H), 6.06 (dd, J=17.6 Hz, 1.2 Hz, 1H), 6.75 (dd, J=17.6 Hz, 10.7 Hz, 1H), 7.14 (d, J=7.8 Hz, 1H), 7.31 (d, J=7.8 Hz, 1H).

[0426] Reaction was carried out in the same manner as in Reference Example 1(c) to obtain a compound of the following Reference Example 4(b).

(b) 3-[(E)-2-(5,6,7,8-tetrahydroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-one

[0427] Appearance; pale yellowish solid

[0428]¹H-NMR (δ, CDCl₃); 1.81-1.95 (m, 4H), 2.79 (t, J=6.1, 2H), 2.96 (t, J=6.4 Hz, 2H), 7.05 (s, 2H), 7.15-7.37 (m, 4H), 7.52-7.64 (m, 4H), 7.81-7.85 (m, 1H), 8.23-8.26 (m, 1H), 8.40 (d, J=2.0 Hz, 1H).

[0429] Reaction was carried out in the same manner as in Reference Example 1(d) to obtain a compound of the following Reference Example 4(c).

(c) 3-[(E)-2-(5,6,7,8-tetrahydroquinolin-2-yl)-ethenyl]-5H-dibenzo[a,d]cyclohepten-5-ol

[0430] Appearance; pale yellowish solid

[0431]¹H-NMR (δ, CDCl₃); 1.80-2.00 (m, 4H), 2.77 (m, 2H), 2.95 (m, 2H), 5.45 (s, 1H), 7.09 (s, 1H), 7.20-7.70 (m, 10H), 7.89 (s, 1H).

Reference Example 5 (a) 3-(7-chloro-6-fluoroquinolin-2-yl)methoxy-5H-dibenzo[a,d]cyclohepten-5-one

[0432] In 30 ml of N,N-dimethylformamide were dissolved 0.37 g (1.4 mmol) of 2-bromomethyl-7-chloro-6-fluoroquinoline and 0.30 g (1.4 mmol) of 3-hydroxy-5H-dibenzo-[a,d]cyclohepten-5-one, and 0.37 g (2.8 mmol) of potassium carbonate was added to the mixture and the resulting mixture was stirred at room temperature for 6 hours.

[0433] After completion of the reaction, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated. The residue was dried under reduced pressure to obtain 0.47 g of the title compound as dark brown solid.

[0434] CI-MS (m/z) ; 416 (M⁺+1) EI-MS; 415 (M⁺). ¹H-NMR (δ, DMSO-d₆); 5.53 (s, 2H), 7.13 (d, J=12.2 Hz, 1H), 7.21 (d, J=12.2 Hz, 1H), 7.51 (dd, J=8.5 Hz, 2.7 Hz, 1H), 7.55-7.90 (m, 6H), 8.00-8.35 (m, 2H), 8.31 (d, J=7.3 Hz, 1H), 8.46 (d, J=8.5 Hz, 1H).

(b) 3-(7-chloro-6-fluoroquinolin-2-yl)methoxy-5H-dibenzo[a,d]cyclohepten-5-ol

[0435] Reaction was carried out in the same manner as in Reference Example 1(d) except for using 3-(7-chloro-6fluoroquinolin-2-yl)methoxy-5H-dibenzo[a,d]cyclohepten-5-one in place of 3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-one to obtain the title compound.

[0436] Appearance; brown solid

[0437] CI-MS (m/z) ; 418 (M⁺+1) EI-MS; 418 (M⁺). ¹H-NMR (δ, DMSO-d₆); 5.38 (s, 1H), 5.41 (s, 2H), 6.80-7.90 (m, 9H), 7.95-8.35 (m, 3H), 8.42 (d, J=8.8 Hz, 1H).

Reference Example 6 (a) 2-methoxycarbonylbenzyltriphenylphosphonium bromide

[0438] In 300 ml of acetonitrile were dissolved 86.32 g (377 mmol) of methyl 2-(bromomethyl)benzoate and 98.84 g (377 mmol) of triphenylphosphine, and the solution was refluxed for 2 hours.

[0439] After completion of the reaction, 700 ml of diethyl ether was added to the reaction mixture. The precipitated white precipitates were collected by filtration and washed with diethyl ether. The precipitates were dried under reduced pressure to obtain 117.42 g of the title compound as pale brown solid.

[0440] CI-MS (m/z); 410 (M⁺−Br). ¹H-NMR (δ, DMSO-d₆); 3.46 (s, 3H), 5.53 (d, J=15.4 Hz, 2H), 7.30-7.40 (m, 1H), 7.45-7.63 (m, 8H), 7.65-7.80 (m, 6H), 7.82-7.95 (m, 4H).

(b) Methyl 2-[2-(4-methoxyphenyl)ethenyl]benzoate

[0441] In 50 ml of acetonitrile were dissolved 4.91 g (10 mmol) of 2-methoxycarbonylbenzyltriphenylphosphonium bromide and 1.77 g (13 mmol) of 4-methoxybenzaldehyde, and 2.48 g (20 mmol) of 1,5-diazabicyclo[4.3.0]-5-nonene was added to the solution and the mixture was refluxed for 5 hours.

[0442] After completion of the reaction, the reaction mixture was concentrated, and the residue was applied to silica gel column chromatography (eluent: toluene) to obtain 1.25 g of the title compound (E,Z mixture) as pale yellowish oily product.

[0443] CI-MS (m/z) ; 269 (M⁺+1). EI-MS; 268 (M⁺).

[0444] Cis isomer (Z isomer) ¹H-NMR (δ, DMSO-d₆); 3.79 (s, 3H), 3.87 (s, 3H), 6.74 (d, J=9.0 Hz, 1H), 6.90-7.00 (m, 2H), 7.10-7.73 (m, 5H), 7.75-7.95 (m, 2H).

[0445] Trans isomer (E isomer) ¹H-NMR (δ, DMSO-d₆); 3.69 (s, 3H), 3.87 (s, 3H), 6.56 (d, J=12.2 Hz, 1H), 6.74 (d, J=9.0 Hz, 1H), 6.84 (d, J=12.2 Hz, 1H), 6.90-7.00 (m, 2H), 7.10-7.73 (m, 3H), 7.75-7.95 (m, 2H).

(c) 2-[2-(4-Methoxyphenyl)ethenyl]benzoic acid

[0446] To 2 ml of a methanol solution containing 1.20 g (4.5 mmol) of methyl 2-[2-(4-methoxyphenyl)ethenyl]benzoic acid was added 1.5 g (26.7 mmol) of an aqueous potassium hydroxide solution (20 ml), and the mixture was refluxed for 6 hours.

[0447] After completion of the reaction, the reaction mixture was cooled and a 1N aqueous hydrochloric acid solution was added to the mixture to adjust a pH thereof to 3. Formed white precipitates were collected by filtration, washed with water and dried under reduced pressure to obtain 1.12 g of the title compound (E,Z mixture) as white solid.

[0448] CI-MS (m/z) ; 255 (M⁺+1) EI-MS; 254 (M⁺).

[0449] Cis isomer (Z isomer) 1H-NMR (δ, DMSO-d₆) ; 3.78 (s, 3H), 6.53 (d, J=12.2 Hz, 1H), 6.74 (d, J=8.8 Hz, 1H), 6.89 (d, J=12.2 Hz, 1H), 6.96 (d, J=8.8 Hz, 1H), 6.97 (d, J=8.8 Hz, 1H), 7.15-7.60 (m, 3H), 7.70-7.95 (m, 2H), 12.93 (br, 1H).

[0450] Trans isomer (E isomer) ¹H-NMR (δ, DMSO-d₆); 3.69 (s, 3H), 6.74 (d, J=8.8 Hz, 1H), 6.96 (d, J=8.8 Hz, 1H), 6.97 (d, J=8.8 Hz, 1H), 7.12 (d, J=16.1 Hz, 1H), 7.15-7.60 (m, 4H), 7.70-7.95 (m, 2H), 12.93 (br, 1H).

(d) 2-[2-(4-Methoxyphenyl)ethyl]benzoic acid

[0451] To 20 ml of a methanol solution containing 0.20 g (1.3 mmol) of 2-[2-(4-methoxyphenyl)ethenyl]benzoic acid was added 0.10 g of 10% palladium-activated charcoal, and then, the mixture was stirred at room temperature for 5 hours under hydrogen atmosphere (normal pressure).

[0452] After completion of the reaction, 10% palladium-activated charcoal was removed from the reaction mixture by filtration by using Celite (tradename), and the filtrate was concentrated to obtain 0.18 g of the title compound as pale yellowish solid.

[0453] CI-MS (m/z); 257 (M⁺+1). EI-MS; 256 (M⁺). ¹H-NMR (δ, DMSO-d₆); 2.70-2.80 (m, 2H), 3.10-3.20 (m, 2H), 3.67 (s, 3H), 6.80-6.90 (m, 2H), 7.10-7.20 (m, 2H), 7.22-7.35 (m, 2H), 7.40-7.50 (m, 1H), 7.75-7.85 (m, 1H), 12.88 (br, 1H).

(e) 3-Methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one

[0454] To 50 ml of a methylene chloride solution containing 1.80 g (7.0 mmol) of 2-[2-(4-methoxyphenyl)ethyl]benzoic acid were added 1.83 ml (13 mmol) of trifluoroacetic anhydride and 0.8 ml (6.3 mmol) of boron trifluoride ethyl ether complex and the mixture was stirred at room temperature for 5 hours.

[0455] After completion of the reaction, the reaction mixture was concentrated, and the residue was applied to silica gel column chromatography (eluent: toluene) to obtain 0.65 g of the title compound as yellow oily product.

[0456] CI-MS (m/z); 239 (M⁺+1). EI-MS; 238 (M⁺). ¹H-NMR (δ, DMSO-d₆); 3.12 (s, 4H), 3.79 (s, 3H), 7.12 (dd, J=8.3 Hz, 2.9 Hz, 1H), 7.28 (d, J=8.3 Hz, 1H), 7.35 (d, J=7.8 Hz, 2H), 7.40 (d, J=2.9 Hz, 1H), 7.51 (dd, J=7.3 Hz, 1.5 Hz, 1H), 7.84 (d, J=8.1 Hz, 1H).

(f) 3-Methoxy-5H-dibenzo[a,d]cyclohepten-5-one

[0457] To 20 ml of a 1,2-dichloroethane solution containing 0.65 g (2.7 mmol) of 3-methoxy-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5-one were added 0.80 g (4.5 mmol) of N-bromosuccineimide and 0.14 g (0.6 mmol) of benzoyl peroxide, and the mixture was refluxed for 3 hours.

[0458] After completion of the reaction, 100 ml of chloroform was added to the reaction mixture and the resulting mixture was washed with 50 ml of an aqueous 1N sodium hydroxide solution. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated. The residue was dissolved in 50 ml of 1,2-dichloroethane, 50 ml of triethylamine was added thereto and the resulting mixture was refluxed for 2 hours.

[0459] After completion of the reaction, the reaction mixture was concentrated, and the residue was applied to silica gel column chromatography (eluent: toluene/ethyl acetate=9/1 (volume ratio)) to obtain 0.57 g of the title compound as brown solid.

[0460] CI-MS (m/z) ; 237 (M⁺+1) EI-MS; 236 (M⁺) ¹H-NMR (δ, DMSO-d₆); 3.90 (s, 3H), 7.12 (d, J=12.2 Hz, 1H), 7.22 (d, J=12.2 Hz, 1H), 7.38 (dd, J=8.5 Hz, 2.9 Hz, 1H), 7.55-7.68 (m, 2H), 7.70-7.80 (m, 3H), 8.13 (d, J=7.6 Hz, 1H).

(g) 3-Hydroxy-5H-dibenzo[a,d]cyclohepten-5-one

[0461] In 100 ml of acetic acid was dissolved 2.03 g (8.6 mmol) of 3-methoxy-5H-dibenzo[a,d]cyclohepten-5-one, 20 ml of 48% hydrobromic acid was added to the solution and the resulting mixture was-refluxed for 10 hours.

[0462] After completion of the reaction, the reaction mixture was poured into 200 ml of ice-water and the formed solid was collected by filtration, washed with water and dried to obtain 1.48 g of the title compound as dark brown solid.

[0463] CI-MS (m/z) ; 223 (M⁺+1) EI-MS; 222 (M⁺). ¹H-NMR (δ, DMSO-d₆); 7.04 (d, J=12.0 Hz, 1H), 7.12 (d, J=12.0 Hz, 1H), 7.19 (dd, J=8.5 Hz, 2.9 Hz, 1H), 7.50-7.64 (m, 3H), 7.67-7.80 (m, 2H), 8.11 (d, J=7.6 Hz, 1H).

Reference Example 7 (a) 3-(4-Methoxybenzylidene)phthalide

[0464] 22.28 g (150 mmol) of phthalic anhydride, 25.0 g (150 mmol) of 4-methoxyphenyl acetate and 2.0 g (24 mmol) of sodium acetate were mixed and the mixture was stirred at 220° C. for 8 hours.

[0465] After completion of the reaction, ethanol was added to the reaction mixture and insoluble material was removed by filtration, and the filtrate was concentrated. The obtained residue was applied to silica gel column chromatography (eluent: toluene/ethyl acetate=9/1 (volume ratio)) to obtain 13.15 g of the title compound as yellowish solid.

[0466] CI-MS (m/z) ; 253 (M⁺+1) EI-MS; 252 (M⁺). ¹H-NMR (5, DMSO-d₆); 3.81 (s, 3H), 6.90 (s, 1H), 7.06 (d, J=8.8 Hz, 1H), 7.64 (t, J=7.3 Hz, 1H), 7.78 (d, J=8.8 Hz, 1H), 7.87 (t, J=7.3 Hz, 1H), 7.95 (d, J=7.8 Hz, 1H), 8.09 (d, J=7.8 Hz, 1H).

(b) 2-[2-(4-Methoxyphenyl)ethyl]benzoic acid

[0467] To 280 ml of an ethanol solution containing 20.0 g (79.3 mmol) of 3-(4-methoxybenzylidene)phthalide were added 16.6 ml (119 mmol) of triethylamine and Raney nickel (available from Kawaken Finechemical, developed nickel catalyst NTD-65, 24 ml), and the resulting mixture was stirred at 80° C. for 2.5 hours under pressure with hydrogen(10 atm).

[0468] After completion of the reaction, the catalyst was removed from the reaction mixture by filtration using Celite (tradename), and the filtrate was concentrated. The obtained residue was dissolved in 200 ml of methylene chloride, washed successively with 100 ml of a 1N aqueous hydrochloric acid solution, and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated. The residue was dried under reduced pressure to obtain 17.2 g of the title compound as white solid. The obtained compound was the same as the compound of Reference Example 6(d).

Reference Example 8 (a) 2-[2-(4-Bromophenyl)ethenyl]-3-fluorobenzoic acid

[0469] To a liquor in which 11.6 g (121 mmol) of sodium t-butoxide had been suspended in 200 ml of N,N-dimethylformamide were added dropwise a solution in which 20.2 g (120 mmol) of methyl 3-fluoro-2-methylbenzoate and 22.3 g (120 mmol) of p-bromobenzaldehyde had been dissolved in 100 ml of dimethylformamide at 5° C. over 1 hour. After completion of dropwise addition, the mixture was stirred at 10° C. for 1 hour, and further stirred at at room temperature overnight.

[0470] After completion of the reaction, 1.0 liter of water was added to the reaction mixture and the resulting mixture was adjusted with conc. hydrochloric acid to pH 3. Precipitated solid was collected by filtration, washed with water and dried under reduced pressure to obtain 25.3 g of the title compound as pale yellowish solid.

[0471]¹H-NMR (δ, CDCl₃); 7.06 (dd, J=16.9 Hz, 1.7 Hz, 1H), 7.38-7.61 (m, 7H), 7.67 (dd, J=7.1 Hz, 1.7 Hz, 1H), 13.28 (b, 1H).

(b) 2-[2-(4-Bromophenyl)ethyl]-3-fluorobenzoic acid

[0472] To 25.3 g (78.8 mmol) of 2-[2-(4-bromophenyl)ethenyl]-3-fluorobenzoic acid were added 6.2 g (199.4 mmol) of red phosphorus, 60 ml of 57% hydroiodic acid and 150 ml of acetic acid, and the mixture was refluxed for 10 hours.

[0473] After cooling by allowing to stand, red phosphorus was further added to the mixture and the mixture was refluxed. Addition of red phosphorus was carried out further two times.

[0474] After completion of the reaction, 1.0 liter of water was added to the reaction mixture, precipitated solid was collected by filtration, water was added to the solid and the mixture was adjusted to pH 12 with an aqueous sodium hydroxide solution, and insoluble material was filtered off. The filtrate was adjusted to pH 3 with conc. hydrochloric acid, precipitated solid was collected by filtration, washed with water and dried under reduced pressure to obtain 23.9 g of the title compound as colorless solid.

[0475]¹H-NMR (δ, CDCl₃); 2.76-2.81 (m, 2H), 3.15-3.20 (m, 2H), 7.16 (d, J=8.3 Hz, 2H), 7.35-7.39 (m, 2H), 7.47 (d, J=8.3 Hz, 2H), 7.65-7.68 (m, 1H), 13.4 (b, 1H).

(c) 3-Bromo-9-fluoro-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-one

[0476] To 25.8 g (80 mmol) of 2-[2-(4-bromophenyl)ethyl]-3-fluorobenzoic acid was added 550 g of polyphosphoric acid, and the mixture was stirred at 170° C. for 3 hours. After cooling the mixture to 80° C. by allowing to stand, water was added to the mixture and the resulting mixture was cooled to room temperature under stirring by allowing to stand.

[0477] After completion of the reaction, the reaction mixture was extracted with chloroform. The extract was washed successively with water, an aqueous sodium hydroxide solution, and water. The organic layer was dried over anhydrous sodium sulfate, concentrated and the residue was applied to silica gel column chromatography (eluent: hexane/ethyl acetate=9/1(volume ratio)) to obtain 18.6 g of the title compound as brown solid.

[0478] CI-MS (m/z) ; 305 (M⁺+1). ¹H-NMR (δ, CDCl₃); 3.11-3.23 (m, 4H), 7.17 (d, J=8.5 Hz, 1H), 7.19-7.34 (m, 2H), 7.55 (dd, J=8.3 Hz, 2.2 Hz, 1H), 7.79 (d, J=7.1 Hz, 1H), 7.99 (m, J=2.2 Hz, 1H).

(d) 3,10,11-Tribromo-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-one

[0479] To 18.1 g (59.2 mmol) of 3-bromo-9-fluoro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one and 21.4 g (120.2 mmol) of N-bromosuccineimide was added 120 ml of 1,2dichloroethane, and the mixture was stirred at 40° C. for 6 hours under mercury lamp irradiation.

[0480] After completion of the reaction, chloroform was added to the reaction mixture, and the resulting mixture was washed with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 28.9 g of the title compound as yellowish solid.

[0481] 1H-NMR (δ, CDCl₃); 5.70 (d, J=5.6 Hz, 1H), 6.14 (d, J=5.9 Hz, 1H), 7.27-7.38 (m, 2H), 7.46-7.53 (m, 1H), 7.69 (dd, J=8.3 Hz, 2.2 Hz, 1H), 7.89-7.92 (m, 1H), 8.17 (d, J=2.2 Hz, 1H).

(e) 3-Bromo-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-one

[0482] After dissolving 8.9 g (20 mmol) of 3,10,11-tribromo-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-one in 50 ml of N,N-dimethylformamide under heating, the solution was cooled, and 14.4 g of sodium hydrosulfite and 18.5 g of sodium hydrogen carbonate was added to the solution and the resulting mixture was stirred at 40° C. for 2 hours.

[0483] After completion of the reaction, warm water was added to the reaction mixture and the mixture was stirred until a temperature thereof became room temperature, and precipitated solid was collected by filtration. The filtrated product was washed with water and dried under reduced pressure to obtain 5.1 g of the title compound as yellowish solid.

[0484]¹H-NMR (δ, CDCl₃); 7.08 (d, J=12.5 Hz, 1H), 7.34-7.44 (m, 3H), 7.47-7.54 (m, 1H), 7.48 (dd, J=8.3 Hz, 2.2 Hz, 1H), 7.93-7.96 (m, 1H), 8.29 (d, J=2.2 Hz, 1H). (f) 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)-ethenyl]-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-one

[0485] In 30 ml of N,N-dimethylformamide were dissolved 2.7 g (13 mmol) of 7-chloro-6-fluoro-2-vinyl quinoline and 3.0 g (10 mmol) of 3-bromo-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-one, and then, 1.0 g (4.6 mmol) of palladium acetate (II), 0.52 g (4.6 mmol) of triphenylphosphine and 2.2 ml (16 mmol) of triethylamine were added to the solution and the resulting mixture was stirred at 100° C. for 4 hours under argon atmosphere.

[0486] After completion of the reaction, the reaction mixture was cooled to room temperature by allowing to stand, 50 ml of ethanol was added to the mixure and the resulting mixture was stirred, and then, precipitated solid was collected by filtration. The collected product by filtration was washed with ethanol to obtain 2.2 g of the title compound as pale green yellowish brown solid.

[0487] CI-MS (m/z) ; 430 (M⁺+1) EI-MS (m/z); 429 (M⁺). ¹H-NMR (δ, DMSO-d₆); 7.40 (s, 2H), 7.66-7.71 (m, 2H), 7.67 (d, J=16.1 Hz, 1H), 7.84 (d, J=8.3 Hz, 1H), 7.91-7.94 (m, 1H), 8.02 (d, J=16.1 Hz, 1H), 8.02 (d, J=9.1 Hz, 1H), 8.03 (d, J=9.8 Hz, 1H), 8.20 (dd, J=8.3 Hz, 1.7 Hz, 1H), 8.23 (d, J=7.8 Hz, 1H), 8.31 (d, J=1.7 Hz, 1H), 8.42 (d, J=8.8 Hz, 1H) (g) 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)-ethenyl]-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-ol

[0488] In 153 ml of tetrahydrofuran was suspended 2.20 g (5.1 mmol) of 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-one, 100 mg (4.6 mmol) of lithium borohydride was added to the suspension under ice-cooling, and the mixture was returned to room temperature and stirred for 1 hour.

[0489] After completion of the reaction, the reaction mixture was ice-cooled and 50 ml of a saturated aqueous sodium hydrogen carbonate solution was poured to the mixture little by little, and after stirring at room temperature for 10 minutes, the resulting mixture was extracted with ethyl acetate. The organic layer was washed with water and further washed with a saturated aqueous sodium chloride solution one time. Then, the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 1.52 g of the title compound as yellowish solid.

[0490] CI-MS (m/z); 432 (M⁺+1). EI-MS (m/z); 431 (M⁺). ¹H-NMR (δ, DMSO-d₆); 5.09 (bs, 1H), 6.36 (bs, 1H), 7.09-7.16 (m, 1H), 7.24 (dd, J=11.5 Hz, 1.5 Hz, 1H), 7.32 (d, J=11.7 Hz, 1H), 7.44-7.52 (m, 3H), 7.59 (d, J=7.8 Hz, 1H), 7.67 (dd, J=8.1 Hz, 1.9 Hz, 1H), 7.93 (d, J=16.1 Hz, 1H) 7.99-8.03 (m, 3H), 8.22 (d, J=7.6 Hz, 1H), 8.38 (d, J=8.5 Hz, 1H).

Reference Example 9

[0491] The reaction was carried out in the same manner as in Reference Example 8(a-g) to obtain the following compounds of Reference Example 9(a-g).

(a) 2-[2-(4-Bromophenyl)ethenyl]-3-chlorobenzoic acid

[0492] Appearance; white solid

[0493]¹H-NMR (δ, CDCl₃) ; 6.72 (d, J=16.6 Hz, 1H), 7.31-7.44 (m, 2H), 7.51-7.61 (m, 4H), 7.66-7.70 (m, 2H), 13.25 (b, 1H).

(b) 2-[2-(4-Bromophenyl)ethyl]-3-chlorobenzoic acid

[0494] Appearance; white solid

[0495] CI-MS (m/z) ; 341 (M⁺+1). ¹H-NMR (δ, CDCl₃); 2.77-2. 83 (m, 2H), 3.22-3.27 (m, 2H), 7.21 (d, J=8.3 Hz, 1H), 7.36 (t, J=7.8 Hz, 1H), 7.50 (d, J=8.5 Hz, 1H), 7.66 (dd, J=8.1 Hz, 2.2 Hz, 1H), 7.75 (dd, J=7.8 Hz, 1.2 Hz, 1H), 13.28 (b, 1H).

(c) 3-Bromo-9-chloro-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-one

[0496] Appearance; yellowish brown solid

[0497] CI-MS (m/z) ; 323 (M⁺+1) ¹H-NMR (δ, CDCl₃); 3. 13-3.17 (m, 2H), 3.31-3.35 (m, 2H), 7.12 (d, J=8.3 Hz, 1H), 7.26 (t, J=8.1 Hz, 1H), 7.52-7.56 (m, 2H), 7.62 (dd, J=7.8 Hz, 1.5 Hz, 1H), 7.97 (d, J=2.2 Hz, 1H).

(d) 3,10,11-Tribromo-9-chloro-5H-dibenzo[a,d]cyclohepten-5-one

[0498] Appearance; pale yellowish solid

[0499]¹H-NMR (δ, CDCl₃); 5.78 (d, J=5.9 Hz, 1H), 6.35 (d, J=5.9 Hz, 1H), 7.31 (d, J=8.3 Hz, 1H), 7.43 (t, J=7.8 Hz, 1H), 7.65 (dd, J=7.8 Hz, 1.2 Hz, 1H), 7.70 (dd, J=8.3 Hz, 2.2 Hz, 1H), 7.92 (dd, J=7.8 Hz, 1.5 Hz, 1H), 8.21 (d, J=2.2 Hz, 1H)

(e) 3-Bromo-9-chloro-5H-dibenzo[a,d]cyclohepten-5-one

[0500] Appearance; pale yellowish solid

[0501] CI-MS (m/z); 321 (M⁺+1). EI-MS (m/z); 320 (M⁺). ¹H-NMR (δ, CDCl₃); 7.10 (d, J=12.5 Hz, 1H), 7.39-7.48 (m, 2H), 7.59 (d,. J=12.7 Hz, 1H), 7.70-7.74 (m, 2H), 7.97 (dd, J=8.1 Hz, 1.2 Hz, 1H), 8.18 (d, J=1.7 Hz, 1H). (f) 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-chloro-5H-dibenzo[a,d]cyclohepten-5one

[0502] Appearance; green yellowish solid

[0503] CI-MS (m/z); 448 (M⁺+1). EI-MS (m/z); 445 (M⁺). ¹H-NMR (δ, DMSO-d₆); 7.52 (d, J=12.5 Hz, 1H), 7.56 (d, J=12.7 Hz, 1H), 7.62-7.69 (m, 2H), 8.82 (d, J=8.3 Hz, 1H), 7.91-8.05 (m, 5H), 8.18-8.25 (m, 3H), 8.42 (d, J=9.0 Hz, 1H). (g) 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)-ethenyl]-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-ol

[0504] Appearance; orange solid

[0505] CI-MS (m/z) ; 448 (M⁺+1) ¹H-NMR (δ, DMSO-d₆); 5.05 (bs, 1H), 6.45 (bs, 1H), 7.37-7.52 (m, 7H), 7.67 (dd, J=8.1 Hz, 1.7 Hz, 1H), 7.69 (d, J=7.3 Hz, 1H), 7.93 (d, J=16.1 Hz, 1H), 7.90-8.02 (m, 2H), 8.21 (d, J=7.3 Hz, 1H), 8.38 (d, J=8.8 Hz, 1H)

Reference Example 10

[0506] The reaction was carried out in the same manner as in Reference Example 8(a-e) to obtain the following compounds of Reference Example 10(a-e).

(a) 2-[2-(4-Bromophenyl)ethenyl]-3-iodobenzoic acid

[0507] Appearance; pale yellowish solid

[0508] CI-MS (m/z) : 428 (M⁺+1) EI-MS (m/z) : 429 (M⁺) ¹H-NMR (8, CDCl₃); 6.51 (d, J=16.6 Hz, 1H), 7.15 (t, J=7.8 Hz, 1H), 7.29 (d, J=16.4 Hz, 1H), 7.53 (d, J=8.5 Hz, 1H), 7.59 (d, J=8.5 Hz, 1H), 7.69 (dd, J=7.8 Hz, 1.2 Hz, 1H), 8.07 (dd, J=7.8 Hz, 1.2 Hz, 1H), 13.28 (b, 1H).

(b) 2-[2-(4-Bromophenyl)ethyl]-3-iodobenzoic acid

[0509] Appearance; white solid

[0510] CI-MS (m/z); 431 (M⁺+1). ¹H-NMR (δ, CDCl₃); 2.75-2.83 (m, 2H), 3.20-3.25 (m, 2H), 7.09 (t, J=7.8 Hz, 1H), 7.24 (d, J=8.3 Hz, 1H), 7.52 (d, J=8.3 Hz, 1H), 7.78 (dd, J=7.8 Hz, 1.5 Hz, 1H), 8.06 (dd, J=7.8 Hz, 1.2 Hz, 1H), 13.3 (b, 1H).

(c) 3-Bromo-9-iodo-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-one

[0511] Appearance; yellowish solid

[0512] CI-MS (m/z); 413 (M⁺+1). ¹H-NMR (δ, CDCl₃); 3.13-3.17 (m, 2H), 3.31-3.33 (m, 2H), 7.01 (t, J=7.8 Hz, 1H), 7.11 (d, J=8.3 Hz, 1H), 7.55 (dd, J=8.1 Hz, 2.2 Hz, 1H), 7.75 (dd, J=7.8 Hz, 1.5 Hz, 1H), 7.98-8.01 (m, 2H).

(d) 3,10,11-Tribromo-9-iodo-5H-dibenzo[a,d]cyclohepten-5-one

[0513] Appearance; yellowish solid

[0514]¹H-NMR (δ, CDCl₃); 5.80 (d, J=5.9 Hz, 1H), 6.17 (d, J=6.1 Hz, 1H), 7.14 (t, J=7.8 Hz, 1H), 7.31 (d, J=8.1 Hz, 1H), 7.71 (dd, J=8.3 Hz, 2.2 Hz, 1H), 8.10 (dd, J=7.8 Hz, 1.2 Hz, 1H), 7.24 (d, J=2.2 Hz, 1H).

(e) 3-Bromo-9-iodo-5H-dibenzo[a,d]cyclohepten-5-one

[0515] CI-MS (m/z); 413 (M⁺+1). ¹H-NMR (δ, CDCl₃); 7.05 (d, J=12.5 Hz, 1H), 7.18 (t, J=7.8 Hz, 1H), 7.35-7.42 (m, 2H), 7.72 (dd, J=8.3 Hz, 2.2 Hz, 1H), 8.00 (dd, J=8.1 Hz, 1.0 Hz, 1H), 8.13 (d, J=2.2 Hz, 1H), 8.21 (dd, J=7.8 Hz, 1.2 Hz, 1H).

(f) 3-Bromo-9-trifluoromethyl-5H-dibenzo[a,d]cyclohepten-5-one

[0516] In 28 ml of N,N-dimethylformamide were suspended 6.2 g (15.1 mmol) of 3-bromo-9-iodo-5H-dibenzo[a,d]cyclohepten-5-one obtained in Reference Example 10(e) and 1.15 g (0.60 mmol) of copper (I) iodide, 11.61 g (60.4 mmol) of fluorosulfonyl(difluoro)methyl acetate was added to the suspendsion, and the resulting mixture was stirred at 80° C. for 21 hours under argon atmosphere.

[0517] After completion of the reaction, the reaction mixture was cooled to room temperature by allowing to stand, diluted with ethyl acetate and precipitated material was filtered off, and the filtrate was successively washed with water and a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, concentrated and the residue was applied to silica gel column chromatography (eluent: hexane/ethyl acetate=9/1(volume ratio)) to obtain 4.0 g of the title compound as pale yellowish solid.

[0518] CI-MS (m/z); 355 (M⁺+1). EI-MS (m/z); 354 (M⁺). ¹H-NMR (δ, DMSO-d₆); 7.14 (d, J=12.5 Hz, 1H), 7.39-7.43 (m, 2H), 7.61 (t, J=8.3 Hz, 1H), 7.75 (dd, J=8.3 Hz, 2.2 Hz, 1H), 7.99 (d, J=7.8 Hz, 1H), 8.15 (d, J=2.2 Hz, 1H) 8.19 (d, J=8.5 Hz, 1H).

[0519] The reaction was carried out in the same manner as in Reference Example 8(f) to obtain the following compound of Reference Example 10(g).

(g) 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)-ethenyl]-9-trifluoromethyl-5H-dibenzo[a,d]cyclohepten-5-one

[0520] Appearance; yellowish solid

[0521] CI-MS (m/z); 482 (M⁺+1). EI-MS (m/z); 479 (M⁺). ¹H-NMR (δ, DMSO-d₆); 7.35 (dd, J=12.5 Hz, 1.7 Hz, 1H), 7.50 (d, J=12.7 Hz, 1H), 7.67 (d, J=16.4 Hz, 1H), 7.79-7.87 (m, 2H), 7.97-8.04 (m, 3H), 8.16-8.24 (m, 5H), 8.42 (d, J=8.8 Hz, 1H).

[0522] The reaction was carried out in the same manner as in Reference Example 8(g) to obtain the following compound of Reference Example 10(h). (h) 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)-ethenyl]-9-trifluoromethyl-5H-dibenzo[a,d]cyclohenpten-5-ol

[0523] Appearance; pale yellowish solid

[0524] CI-MS (m/z): 482 (M⁺+1). ¹H-NMR (δ, DMSO-d₆); 5.05 (bs, 1H), 6.53 (bs, 1H), 7.32-7.69 (m, 7H), 7.94 (d, J=16.4 Hz, 1H), 7.99-8.02 (m, 3H), 8.10 (d, J=6.8 Hz, 1H), 8.21 (d, J=7.6 Hz, 1H), 8.79 (d, J=8.8 Hz, 1H).

Reference Example 11

[0525] The reaction was carried out in the same manner as in Reference Example 8(f) to obtain the following compound of Reference Example 11(a).

(a) 3-[(E)-2-(5,6,7,8-tetrahydroquinolin-2-yl)-ethenyl]-9-trifluoromethyl-5H-dibenzo[a,d]cyclohepten-5one

[0526] Appearance; brown solid

[0527] CI-MS (m/z); 432 (M⁺+1). ¹H-NMR (δ, DMSO-d₆); 1.74-1.92 (m, 4H), 2.72-2.87 (m, 4H), 7.31 (dd, J=12.7 Hz, 2.2 Hz, 1H), 7.36-7.53 (m, 4H), 7.66-7.83 (m, 3H), 8.07 (dd, J=8.0 Hz, 1.7 Hz, 1H), 8.11-8.21 (m, 3H).

[0528] The reaction was carried out in the same manner as in Reference Example 8(g) to obtain the following compound of Reference Example 11(b).

(b) 3-[(E)-2-(5,6,7,8-tetrahydroquinolin-2-yl)-ethenyl]-9-trifluoromethyl-5H-dibenzo[a,d]cyclohepten-5-ol

[0529] Appearance; gray solid

[0530] CI-MS (m/z); 434. (M⁺+1). ¹H-NMR (δ, DMSO-d₆); 1.75-1.85 (m, 4H), 2.72-2.86 (m, 4H), 5.03 (bs, 1H), 6.46 (bs, 1H), 7.27 (d, J=16.1 Hz, 1H), 7.33-7.46 (m, 4H), 7.54-7.67 (m, 3H), 7.94 (s, 1H) 8.08 (d, J=7.3 Hz, 1H).

Reference Example 12 (a) 2-Chloro-6-methylbenzoic acid

[0531] To a liquid in which 42.5 g (0.43 mol) of copper (I) chloride had been suspended in 700 ml of acetonitrile was: added 39.9 g (0.39 mol) of t-butyl nitrite, and the mixture was warmed to 55° C. To the liquor was added 40.0 g (0.26 mol) of 2-amino-6-methylbenzoic acid by dividing into portions. After stirring at 60° C. for 3 hours, the mixture was cooled to room temperature by allowing to stand.

[0532] After completion of the reaction, the reaction mixture was poured into a mixed solution of 1.5 liters of conc. hydrochloric acid and 1.5 liters of water, and extracted with chloroform. The organic layer was washed with a saturated aqueous ammonium chloride solution, and dried over anhydrous magnesium sulfate. The concentrate concentrated under reduced pressure was recrystallized from cyclohexane to obtain 21.8 g of the title compound as beige color solid.

[0533] CI-MS (m/z); 171 (M⁺+1). ¹H-NMR (δ, CDCl₃); 2.45 (s, 3H), 7.15 (t, J=4.2 Hz, 1H), 7.26-7.28 (m, 2H), 9.94 (bs, 1H).

(b) Methyl 2-chloro-6-methylbenzoate

[0534] In 10 ml of N,N-dimethylformamide was dissolved 1.8 g (10.6 mmol) of 2-chloro-6-methylbenzoic acid, and then, 1.49 g (10.8 mmol) of potassium carbonate and 2.7 ml of methyl iodide were added to the solution, and the mixture was stirred at room temperature for 3 hours.

[0535] After completion of the reaction, water was added to the reaction mixture and the mixture was extracted with diethyl ether. The organic layer was successively washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was applied to silica gel column chromatography (eluent: hexane/ethyl acetate=9/l(volume ratio)) to obtain 1.69 g of the title compound as pale yellowish liquid.

[0536] CI-MS (m/z); 171 (M⁺+1) ¹H-NMR (δ, CDCl₃); 2.32 (s, 3H), 3.95 (s, 3H), 7.10 (t, J=4.3 Hz, 1H), 7.22-7.23 (m, 2H).

(c) Methyl 2-chloro-6-bromomethylbenzoate

[0537] To 20.0 g (108 mmol) of methyl 2-chloro-6-methylbenzoate and 19.3 g (108 mmol) of N-bromosuccineimide was added 100 ml of 1,2-dichloroethane, and the mixture was stirred at 50° C. for 5 hours under mercury lamp irradiation.

[0538] After completion of the reaction, chloroform was added to the reaction mixture and the resulting mixture was washed with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and hexane was added to the residue and precipitated material was removed by filtration. The filtrate was concentrated under reduced pressure to obtain 27.6 g of the title compound as pale yellowish liquid.

[0539]¹H-NMR (δ, CDCl₃); 4.00 (s, 3H), 4.50 (s, 2H), 7.32-7.39 (m, 3H).

(d) 3-Chloro-2-methoxycarbonylbenzyltriphenylphosphonium bromide

[0540] To a mixture of 27.6 g of methyl 2-chloro-6-bromomethylbenzoate and 39.0 g of triphenylphosphine was added 200 ml of acetonitrile, and the mixture was stirred at 80° C. for 3 hours.

[0541] After completion of the reaction, the reaction mixture was concentrated under reduced pressure and diethyl ether was added to the residue. The precipitated solid was collected by filtration and dried under reduced pressure to obtain 44.6 g of the title compound as beige color solid.

[0542]¹H-NMR (δ, CDCl₃); 3.66 (s, 3H), 5.62 (d, J=2.0 Hz, 2H), 7.32-7.39 (m, 18 H).

(e) Methyl 6-[2-(4-bromophenyl)ethenyl]-2-chlorobenzoate

[0543] To a mixture of. 44.6 g (84.9 mmol) of 3-chloro-2-methoxycarbonylbenzyltriphenylphosphonium bromide and 16.7 g (90.4 mmol) of 4-bromobenzaldehyde was added 150 ml of acetonitrile, and then, 14.8 g (119 mmol) of 1,5-diazabicyclo[4,3,0]-5-nonene was added dropwise to the mixture. Thereafter, the mixture was refluxed for 3 hours.

[0544] After completion of the reaction, the reaction mixture was concentrated under reduced pressure, ethyl acetate was added to the residue and insoluble material was removed by filtration. The filtrate was successively washed with a 5% aqueous potassium hydrogen sulfate solution, a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution in this order. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was applied to silica gel column chromatography (eluent: hexane/ethyl acetate=9/1 (volume ratio)) to obtain 27.6 g of the title compound as colorless liquid.

[0545]¹H-NMR (δ, CDCl₃); 3.95, 4.08 (each s, 3H in total), 6.61 (dd, J=12.2 Hz, 2.2 Hz, 1H), 6.97-7.17 (m, 3H), 7.28-7.58 (m, 6H).

[0546] Reaction was carried out in the same manner as in Reference Example 8(b) to obtain a compound of the following Reference Example 12(f).

(f) 6-[2-(4-Bromophenyl)ethyl]-2-chlorobenzoic acid

[0547] Appearance; white solid

[0548] CI-MS (m/z); 339 (M⁺+1). ¹H-NMR (δ, CDCl₃); 2.84-2.98 (m, 4H), 6.99-7.06 (m, 2H), 7.26-7.29 (m, 3H), 7.35-7.39 (m, 2H).

[0549] The reaction was carried out in the same manner as in Reference Example 8(c) to obtain the following compound of Reference Example 12(g).

(g) 3-Bromo-6-chloro-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-one

[0550] Appearance; beige color solid

[0551] CI-MS (m/z): 323 (M⁺+1). ¹H-NMR (δ, CDCl₃); 3.06-3.11 (m, 2H), 3.16-3.20 (m, 2H), 7.08 (d, J=8.3 Hz, 1H), 7.14 (dd, J=6.8 Hz, 1.7 Hz, 1H), 7.26-7.31 (m, 2H), 7.54 (dd, J=8.3 Hz, 2.4 Hz, 1H), 8.01 (d, J=2.2 Hz, 1H).

[0552] The reaction was carried out in the same manner as in Reference Example 8(d) to obtain the following compound of Reference Example 12 (h).

(h) 3,11-Dibromo-6-chloro-10-hydro-5H-dibenzo[a,d]-cyclohepten-5-one

[0553] Appearance; yellowish brown foamy solid.

[0554]¹H-NMR (δ, CDCl₃); 3.37 (dd, J=14.9 Hz, 6.6 Hz, 1H), 3.74 (dd, J=14.9 Hz, 2.4 Hz, 1H), 5.56-5.74 (m, 1H), 7.19 (dd, J=7.3 Hz, 1.2 Hz, 1H), 7.33-7.43 (m, 3H), 7.68 (dd, J=8.3 Hz, 2.2 Hz, 1H), 8.98 (d, J=2.0 Hz, 1H).

(i) 3-Bromo-6-chloro-5H-dibenzo[a,d]cyclohepten-5-one

[0555] In 300 ml of ethyl acetate was dissolved 33.0 g of 3,11-dibromo-6-chloro-10-hydro-5H-dibenzo[a,d]cyclohepten-5-one obtained in Reference Example 12(h), and 150 ml of triethylamine was added to the solution and the resulting mixture was stirred at 80° C. for 90 minutes.

[0556] After completion of the reaction, the reaction mixture was cooled to room temperature by allowing to stand, and the mixture was concentrated under reduced pressure. Ethyl acetate was added to the residue, and the mixture was successively washed with a 5% aqueous potassium hydrogen sulfate solution, a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution in this order. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was applied to silica gel column chromatography (eluent: toluene) to obtain 8.91 g of the title compound as brown solid.

[0557] CI-MS (m/z); 321 (M⁺+1). ¹H-NMR (δ, CDCl₃); 6.98 (d, J=12.0 Hz, 1H), 7.04 (d, J=12.2 Hz, 1H), 7.35 (d, J=8.3 Hz, 1H), 7.41-7.47 (m, 2H), 7.57 (dd, J=7.3 Hz, 2.0 Hz, 1H), 7.68 (dd, J=8.3 Hz, 2.2 Hz, 1H), 8.98 (d, J=2.0 Hz, 1H).

[0558] The reaction was carried out in the same manner as in Reference Example 8(f) to obtain a compound of the following Reference Example 12(j).

(j) 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)-ethenyl]-6-chloro-5H-dibenzo[a,d]cyclohepten-5-one

[0559] Appearance; yellowish brown solid

[0560]¹H-NMR (δ, DMSO-d₆); 7.25 (d, J=12.0 Hz, 1H), 7.30 (d, J=12.2 Hz, 1H), 7.62-7.77 (m, 5H), 8.00-8.04 (m, 4H), 8.13 (dd, J=8.3 Hz, 2.0 Hz, 1H), 8.22 (d, J=7.3 Hz, 1H), 8.41 (d, J=8.8 Hz, 1H).

[0561] The reaction was carried out in the same manner as in Reference Example 8(g) to obtain the following compound of Reference Example 12(k).

(k) 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)-ethenyl]-6-chloro-5H-dibenzo[a,d]cyclohepten-5-ol

[0562] Appearance; beige color solid

[0563] 1H-NMR (δ, DMSO-d₆); 5.19 (d, J=3.7 Hz, 1H), 6.49-6.53 (m, 2H), 7.10 (d, J=11.7 Hz, 1H), 7.15 (d, J=12.0 Hz, 1H), 7.35 (t, J=7.8 Hz, 1H), 7.48-7.56 (m, 3H), 7.59 (d, J=2.4 Hz, 1H), 7.70 (dd, J=8.1 Hz, 1.5 Hz, 1H), 7.85 (s, 1H), 7.95 (d, J=16.4 Hz, 1H), 7.97-8.03 (m, 3H), 8.22 (d, J=7.3 Hz, 1H), 8.40 (d, J=8.8 Hz, 1H).

Reference Example 13 (a) 3-Bromo-8-chloro-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-one

[0564] The title compound was obtained as a by-product of Reference Example 12(g).

[0565] Appearance; beige color solid

[0566] CI-MS (m/z) : 323 (M⁺+1) ¹H-NMR (δ, CDCl₃); 3.16 (s, 4H), 7.12 (d, J=8.3 Hz, 1H), 7.24 (d, J=2.2 Hz, 1H), 7.32 (dd, J=8.5 Hz, 2.0 Hz, 1H), 7.55 (dd, J=8.1 Hz, 2.2 Hz, 1H), 7.98 (d, J=8.3 Hz, 1H), 8.15 (d, J=2.2 Hz, 1H).

[0567] The reaction was carried out in the same manner as in Reference Example 8(d) to obtain the following compound of Reference Example 13(b).

(b) 3,10,11-Tribromo-8-chloro-5H-dibenzo[a,d]cyclohepten-5-one

[0568] Appearance; yellowish brown solid

[0569]¹H-NMR (δ, CDCl₃); 5.66 (d, J=5.6 Hz, 1H), 5.70 (d, J=5.6 Hz, 1H), 7.27 (d, J=8.3 Hz, 1H), 7.40 (d, J=2.2 Hz, 1H), 7.47 (dd, J=8.3 Hz, 2.0 Hz, 1H), 7.69 (dd, J=8.1 Hz, 2.2 Hz, 1H), 8.06 (d, J=8.5 Hz, 1H), 8.23 (d, J=2.2 Hz, 1H).

[0570] The reaction was carried out in the same manner as in Reference Example 8(e) to obtain the following compound of Reference Example 13(c).

(c) 3-Bromo-8-chloro-5H-dibenzo[a,d]cyclohepten-5one

[0571] Appearance; beige color solid

[0572] 1H-NMR (δ, CDCl₃); 6.96 (d, J=12.1 Hz, 1H), 7.03 (d, J=12.1 Hz, 1H), 7.41 (d, J=8.3 Hz, 1H), 7.51 (dd, J=8.3 Hz, 2.0 Hz, 1H), 7.53 (d, J=2.0 Hz, 1H), 7.74 (dd, J=8.3 Hz, 2.2 Hz, 1H), 8.16 (d, J=8.4 Hz, 1H), 8.36 (d, J=2.2 Hz, 1H).

[0573] The reaction was carried out in the same manner as in Reference Example 8(f) to obtain the following compound of Reference Example 13(d).

(d) 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)-ethenyl]-8-chloro-5H-dibenzo[a,d]cyclohepten-5-one

[0574] Appearance; green-yellowish brown solid

[0575]¹H-NMR (δ, DMSO-d₆); 7.25 (d, J=12.0 Hz, 1H), 7.35 (d, J=12.2 Hz, 1H), 7.66 (d, J=6.4 Hz, 1H), 7.71 (dd, J=8.5 Hz, 2.2 Hz, 1H), 7.84 (d, J=8.3 Hz, 1H), 7.93 (d, J=2.2 Hz, 1H), 7.99-8.04 (m, 3H), 8.15 (d, J=8.8 Hz, 1H), 8.19-8.24 (m, 2H), 8.38 (d, J=1.7 Hz, 1H), 8.41 (d, J=9.0 Hz, 1H).

[0576] The reaction was carried out in the same manner as in Reference Example 8(g) to obtain the following compound of Reference Example 13(e).

(e) 3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)-ethenyl]-8-chloro-5H-dibenzo[a,d]cyclohepten-5-ol

[0577] Appearance; orange solid

[0578]¹H-NMR (δ, DMSO-d₆); 5.08 (d, J=4.2 Hz, 1H), 6.32 (b, 1H), 7.15 (d, J=11.5 Hz, 1H), 7.24 (d, J=11.7 Hz, 1H), 7.44-7.52 (m, 4H), 7.66 (dd, J=8.1 Hz, 2.0 Hz, 1H), 7.75 (d, J=9.0 Hz, 1H), 7.59 (d, J=16.4 Hz, 1H), 7.99-8.02 (m, 3H), 8.21 (d, J=7.3 Hz, 1H), 8.38 (d, J=8.8 Hz, 1H). 

1. A dibenzocycloheptene compound represented by the formula (I):

wherein R¹ represents a hydrogen atom, a halogen atom, a hydroxy group, a nitro group, a cyano group, a carbamoyl group, a formyl group, a carboxyl group, 1H-tetrazol-5-yl group, C₁-C₄ alkyl group, fluoro C₁-C₄ alkyl group, hydroxy C₁-C₄ alkyl group, C₂-C₄ alkenyl group, C₂-C₄ alkynyl group, C₁-C₄ alkoxy group, fluoro C₁-C₄ alkoxy group, C₁-C₄ alkylthio group, C₁-C₄ alkylsulfinyl group or C₁-C₄ alkylsulfonyl group, R² represents a hydrogen atom, a halogen atom, a nitro group, a cyano group, C₁-C₄ alkyl group or C₁-C₄ alkoxy group, A represents a 5-membered or 6-membered heteroaromatic ring group having 1 to 3 hetero atom(s) selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom or a heteroaromatic ring-fused group in which the heteroaromatic ring group and a benzene ring are fused, and the heteroaromatic ring group or fused heteroaromatic ring group may have a halogen atom, a nitro group, a cyano group, C₁-C₄ alkyl group, fluoro C₁-C₄ alkyl group, C₁-C₄ alkoxy group, fluoro C₁-C₄ alkoxy group, C₁-C₄ alkylthio group or C₃-C₄ alkylene group as a substituent(s), B represents a formula: —CH═CH—, a formula: —CH₂O—, a formula: —CH₂CH₂—, a formula: —CH₂S—, a formula: —OCH₂— or a formula: —SCH₂—, X represents, an oxygen atom, a sulfur atom, a methylene group or a formula: ═CH—, Y represents a C₁-C₁₀ alkylene group which may have a halogen atom, C₁-C₄ alkyl group or C₁-C₄ alkoxy group as a substituent(s), or a group (a) of the formula:

where o and p are each an integer of 0 to 2, and q is an integer of 1 to 4, Z represents a carboxyl group which may be protected; 1H-tetrazol-5-yl group; a formula: —NH—SO₂—R³; or a formula: —CO—NH—SO₂—R where R³ represents a C₁-C₄ alkyl group, a fluoro-C₁-C₄ alkyl group or a phenyl group which may have a halogen atom, a C₁-C₄ alkyl group, a fluoro-C₁-C₄ alkyl group, a C₁-C₄ alkoxy group, a fluoro-C₁-C₄ alkoxy group, a nitro group or a cyano group as a substituent(s), m is an integer of 1 to 4, when m is 2 or more, a plural number of R¹ may be different from each other, n is an integer of 1 to 3, and when n is 2 or more, a plural number of R² may be different from each other,

represents a single bond or a double bond, or a pharmaceutically acceptable salt thereof.
 2. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R¹ of the compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a nitro group, a cyano group, a formyl group, a 1H-tetrazol-5-yl group, a methyl group, a difluoromethyl group, a trifluoromethyl group, a hydroxymethyl group, a 1-hydroxy-1-methylethyl group, a vinyl group, an ethynyl group, a methoxy group, a difluoromethoxy group, a trifluoromethoxy group, a methylthio group, a methylsulfinyl group and a methylsulfonyl group.
 3. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R¹ of the compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a cyano group, a trifluoromethyl group, a hydroxymethyl group, a 1-hydroxy-1-methylethyl group, an ethynyl group, a methoxy group, a difluoromethoxy group, a trifluoromethoxy group, a methylsulfinyl group and a methylsulfonyl group.
 4. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, wherein R² of the compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group and a methoxy group.
 5. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, wherein R² of the compound represented by the formula (I) is a hydrogen atom.
 6. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, wherein A of the compound represented by the formula (I) is selected from the group consisting of 2-pyridyl, 2benzothiazolyl, quinolin-2-yl, 5,6-difluoro-2-pyridyl, 5,6dichloro-2-pyridyl, 5,6-dimethyl-2-pyridyl, 5,6,7,8-tetrahydroquinolin-2-yl, 6-fluoro-2-benzothiazolyl, 5fluoro-2-benzothiazolyl, 5,6-difluoro-2-benzothiazolyl, 6-chloro-2-benzothiazolyl, 5-chloro-2-benzothiazolyl, 5,6-dichloro-2-benzothiazolyl, 5-chloro-6-fluoro-2-benzothiazolyl, 5-methyl-2-benzothiazolyl, 5-cyano-2-benzothiazolyl, 5-trifluoromethyl-2-benzothiazolyl, 5-methylthio-2-benzothiazolyl, 5-fluoroquinolin-2-yl, 6-fluoroquinolin-2-yl, 7-fluoroquinolin-2-yl, 5-chloroquinolin-2-yl, 6-chloroquinolin-2-yl, 7-chloroquinolin-2-yl, 7-methylquinolin-2-yl, 7-trifluoromethylquinolin-2-yl, 7-methoxyquinolin-2-yl, 7-difluoromethoxyquinolin-2-yl, 7-trifluoromethoxyquinolin-2-yl, 5,7-difluoroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 5,7-dichloroquinolin-2-yl, 6,7-dichloroquinolin-2-yl, 5-chloro-7-fluoroquinolin-2-yl, 6chloro-7-fluoroquinolin-2-yl, 7-chloro-5-fluoroquinolin-2yl, 7-chloro-6-fluoroquinolin-2-yl, 7-chloro-6-cyanoquinolin-2-yl, 7-cyano-6-fluoroquinolin-2-yl, 6-fluoro-7trifluoromethylquinolin-2-yl and 5,6,7-trifluoroquinolin-2-yl group.
 7. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, wherein A of the compound represented by the formula (I) is selected from the group consisting of 5,6,7,8-tetrahydroquinolin-2-yl, 7-fluoroquinolin-2-yl, 7-chloroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 6,7-dichloroquinolin-2-yl and 7-chloro-6-fluoroquinolin-2-yl group.
 8. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, wherein B of the compound represented by the formula (I) is a formula: —CH═CH—, a formula: —OCH₂— or a formula: —CH₂O—.
 9. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 8, wherein X of the compound represented by the formula (I) is an oxygen atom or a sulfur atom.
 10. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 9, wherein Y of the compound represented by the formula (I) is selected from the group consisting of methylene, ethylene, trimethylene, difluoromethylene, 1-fluoroethylene, 2fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, ethylidene, 1-methylethylene, 2-methylethylene, 2,2-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene and (a-5) group.
 11. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 9, wherein Y of the compound represented by the formula (I) is selected from the group consisting of methylene, ethylene, trimethylene, ethylidene, 1-methylethylene, 2-methylethylene and (a-5) group.
 12. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 11, wherein Z of the compound represented by the formula (I) is selected from the group consisting of carboxyl, methanesulfonylamino, trifluoromethanesulfonylamino, methanesulfonylaminocarbonyl and trifluoromethanesulfonylaminocarbonyl group.
 13. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 11, wherein Z of the compound represented by the formula (I) is a carboxyl group.
 14. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 13, wherein m of the compound represented by the formula (I) is 1 or
 2. 15. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 14, wherein n of the compound represented by the formula (I) is
 1. 16. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R¹ of the compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a nitro group, a cyano group, a formyl group, a 1H-tetrazol-5-yl group, a methyl group, a difluoromethyl group, a trifluoromethyl group, a hydroxymethyl group, a 1-hydroxy-1-methylethyl group, a vinyl group, an ethynyl group, a methoxy group, a difluoromethoxy group, a trifluoromethoxy group, a methylthio group, a methylsulfinyl group and a methylsulfonyl group, R² is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group and a methoxy group, A is selected from the group consisting of 5,6,7,8-tetrahydroquinolin-2-yl, 7-fluoroquinolin-2-yl, 7-chloroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 6,7-dichloroquinolin-2-yl and 7-chloro-6-fluoroquinolin-2-yl group, B is a formula: —CH═CH—, a formula: —OCH₂— or a formula: —CH₂O—, X is an oxygen atom or a sulfur atom, Y is selected from the group consisting of methylene, ethylene, trimethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, ethylidene, 1-methylethylene, 2-methylethylene, 2,2-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene and (a-5) group, Z is selected from the group consisting of carboxy, methanesulfonylamino, trifluoromethanesulfonylamino, methanesulfonylaminocarbonyl and trifluoromethanesulfonylaminocarbonyl group, m is 1 or 2, and n is
 1. 17. The dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R¹ of the compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a cyano group, a trifluoromethyl group, a hydroxymethyl group, a 1-hydroxy-1-methylethyl group, an ethynyl group, a methoxy group, a difluoromethoxy group, a trifluoromethoxy group, a methylsulfinyl group and a methylsulfonyl group, R² is a hydrogen atom, A is selected from the group consisting of a 5,6,7,8-tetrahydroquinolin-2-yl, 7-fluoroquinolin-2-yl, 7-chloroquinolin-2-yl, 6,7-difluoroquinolin-2-yl, 6,7-dichloroquinolin-2-yl and 7-chloro-6-fluoroquinolin-2-yl group, B is a formula: —CH═CH—, a formula: —OCH₂— or a formula: —CH₂O—, X is an oxygen atom or a sulfur atom, Y is selected from the group consisting of a methylene, ethylene, trimethylene, ethylidene, 1-methylethylene, 2-methylethylene and (a-5) group, Z is a carboxy group, m is 1 or 2, and n is
 1. 18. The dibenzocycloheptene compound or a pharmaceutically acceptable-salt thereof according to claim 1, wherein the compound represented by the formula (I) is selected from the group consisting of: [3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetic acid, 3-{[3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}-2methylpropionic acid, 3-{[3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid, 3-{[3-[(E)-2-(6,7-difluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}-2-methylpropionic acid, [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetic acid, 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)-ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}propionic acid, 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}-2-methylpropionic acid, [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thioacetic acid, 2-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid, 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid, 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thiomethyl}cyclopropane acetic acid, [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-fluoro-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetic acid, 3-{[3-[(E) -2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-fluoro-5H-dibenzo[a,d]cyclohepten-5yl]thio}propionic acid, [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetic acid, 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid, 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-8-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid, [3-[(E) -2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-6-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetic acid, 2-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}propionic acid, 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-6-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]oxy}propionic acid, [3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-6-chloro-5H-dibenzo[a,d]cyclohepten-5-yl]thioacetic acid, 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-6-chloro-5H-dibenzo[a,d]cyclopten-5yl]thio}propionic acid, 3-{[3-[(E)-2-(7-chloro-6-fluoroquinolin-2-yl)ethenyl]-9-trifluoromethyl-5H-dibenzo[a,d]cyclohepten-5-yl]-thio}propionic acid, 3-{[3-(7-chloro-6-fluoroquinolin-2-yl)methoxy-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid, [3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]oxyacetic acid, [3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thioacetic acid, 3-{[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid, 3-{[3-[(E)-2-(5,6,7,8-tetrahydroquinolin-2-yl)ethenyl]-5H-dibenzo[a,d]cyclohepten-5-yl]thio}propionic acid and or 3-{[3-[(E)-2-(5,6,7,8-tetrahydroquinolin-2-yl)ethenyl]-9-trifluoromethyl-5H-dibenzo[a,d]cyclohepten-5yl]thio}-propionic acid.
 19. A medical composition containing the dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 18 as an effective ingredient.
 20. The medical composition according to claim 19, wherein the medical composition is a composition for prophylaxis or treatment of asthma, allergic diseases and/or inflammatory diseases.
 21. Use of the dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 18 for the preparation of a medical composition.
 22. Use according to claim 21, wherein the medical composition is a composition for prophylaxis or treatment of asthma, allergic diseases and/or inflammatory diseases.
 23. A method of prophylaxis or treatment of disease which comprises administering the dibenzocycloheptene compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 18 to a warm-blooded animal with a pharmaceutically effective amount.
 24. The method according to claim 23, wherein the disease is asthma, allergic diseases and/or inflammatory diseases.
 25. The method according to claim 23 or 24, wherein the warm-blooded animal is human. 